Submissions for variant Single allele

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Total submissions: 1772

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Monogenic Diabetes Variant Curation Expert Panel	RCV001843396	SCV002102526	uncertain significance	Monogenic diabetes	2022-02-17	reviewed by expert panel	curation	The c.-287G>A variant in the HNF1 homeobox A gene, HNF1A, is located in the promoter of NM_000545.8. This region is defined as critical for the protein’s function by the ClinGen MDEP (PM1_Supporting) and is absent from gnomAD v2.1.1 (PM2_Supporting). Additionally, the c.-287G>A variant was identified in at least one individual with a clinical history highly specific for HNF1A-MODY (MODY probability calculator result >50%, negative genetic testing for HNF4A, and response to low doses of sulfonylurea) (PP4_Moderate; PMID: 23348805). In summary, c.-287G>A meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/21): PM1_supporting, PM2_Supporting, PP4_Moderate.
ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen	RCV002221974	SCV002499284	pathogenic	Familial cancer of breast	2022-03-09	reviewed by expert panel	curation	The ATM EX27del variant is absent from gnomAD SVs v2.1 (PM2_supporting). This variant is expected to produce an NMD-prone transcript due to a nonsense or frameshifting event (PVS1). In the absence of potential splicing rescue mechanisms in ATM, all PVS1-eligble truncating variants are expected to be pathogenic based on the existence of known pathogenic C-terminal truncations in the last exon (PM5_Supporting). This variant is absent from gnomAD SVs v2.1 (PM2_Supporting). In summary, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP criteria applied as specified by the HBOP Variant Curation Expert Panel
ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Variant Curation Expert Panel, ClinGen	RCV002221975	SCV002499295	likely pathogenic	Familial cancer of breast	2022-03-09	reviewed by expert panel	curation	The ATM EX16_60dup variant is presumed to be a tandem duplication and results in the disruption of a critical domain (PVS1_Strong). The variant is absent in the GnomAD v2.1.1 cohort (PM2_Supporting). This variant has been observed in a compound heterozygous state (confirmed) in one individual with Ataxia-Telangiectasia (PM3, GTR Lab ID: 500031). In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the HBOP Variant Curation Expert Panel.
ClinGen Monogenic Diabetes Variant Curation Expert Panel	RCV002222111	SCV002499532	uncertain significance	Monogenic diabetes	2022-04-12	reviewed by expert panel	curation	The c.-286_-285del variant in the HNF1 homeobox A gene, HNF1A, is located in the promoter of NM_000545.8. This region is defined as critical for the protein’s function by the ClinGen MDEP (PM1_Supporting) and is absent from gnomAD v2.1.1 (PM2_Supporting). This variant was identified in an individual with a clinical history suggestive of HNF1A-MODY (MODY probability calculator result nearly 50%); however, HNF4A was not tested (internal lab contributors), and therefore PP4 was not applied. In summary, c.-286_-285del meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/21): PM1_supporting, PM2_Supporting.
ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel	RCV003149088	SCV003836617	pathogenic	Familial adenomatous polyposis 1	2023-02-26	reviewed by expert panel	curation	The NC_000005.10:g.(?_112707312)_(112707902_?)del variant in APC is a gross deletion in the 5' upstream region of APC impacting promoter 1B. This variant has been reported in many families with FAP, resulting in more than 16 phenotype points (PS4_VeryStrong; Ambry Genetics, Invitae, GeneDx, Bonn internal data, PMIDs 18982352, 26213617, 25941542, 24946964, 23725351, 27217144, 18433509, 28791770, 25243319). The variant has been reported to segregate with FAP in many members (more than 7) of multiple families (PP1_Strong; PMIDs 18982352, 25941542, 23725351, 18433509, 28791770, 25243319). This variant has also been identified as a de novo occurrence with unconfirmed parental relationships in one individual with FAP (PM6; PMID 27217144). RT-PCR, allele-specific PCR and quantitative RT-PCR assays show monoallelic expression of various SNPs and severely reduced RNA expression of APC transcripts supporting an allele silencing effect for this deletion (PS3_VeryStrong; PMIDs 18982352, 25941542, 24946964, 27217144, 18433509, 28791770 25243319). This variant is absent from gnomAD SVs v2.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for FAP based on the ACMG/AMP criteria applied, as specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel: PS3_VeryStrong, PS4_VeryStrong, PP1_Strong, PM6, and PM2_Supporting (VCEP specifications version 1; date of approval: 12/12/2022).
ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel	RCV003149089	SCV003836618	likely pathogenic	Familial adenomatous polyposis 1	2023-02-26	reviewed by expert panel	curation	The NC_000005.10:g.(?_112775619)_(112801393_?)del variant in APC is a deletion predicted to result in an out-of-frame deletion of exons 5-8 in a gene in which loss-of-function is an established disease (PVS1). This variant is absent from gnomAD SVs v2.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as of Likely Pathogenic for FAP based on the ACMG/AMP criteria applied, as specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel: PVS1, PM2_Supporting (VCEP specifications version 1; date of approval: 12/12/2022).
ClinGen Monogenic Diabetes Variant Curation Expert Panel	RCV003326070	SCV004032066	uncertain significance	Monogenic diabetes	2023-08-18	reviewed by expert panel	curation	The c.-181G>T p.(?) variant in the hepatocyte nuclear factor 4-alpha gene, HNF4A, is located within the promoter region of HNF1A/HNF1B binding sites, which is defined as critical for the protein’s function by the ClinGen MDEP (PM1_Supporting). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant was identified in an individual with diabetes; however, the MODY probability could not be calculated due to missing information, and PP4 was not met. In addition, the c.-181G>A p.(?) variant at the same nucleotide has been classified as pathogenic for monogenic diabetes by the ClinGen MDEP (PS1_Supporting). In summary, c.-181G>T p.(?) meets the criteria to be classified as a VUS for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP VCEP (specification version 1.1.0, approved 8/11/2023): PM1_Supporting, PM2_Supporting, PS1_Supporting.
ClinGen Myeloid Malignancy Variant Curation Expert Panel	RCV003448645	SCV004176242	pathogenic	Hereditary thrombocytopenia and hematologic cancer predisposition syndrome	2023-12-09	reviewed by expert panel	curation	NC_000021.9:g.(?_34787801)_(35048958_?)del results in the complete absence of the coding sequence of the RUNX1 gene and therefore the absence of all functional domains. The deletion is not present in population databases. In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PM1 and PM2_supporting.
ClinGen Myeloid Malignancy Variant Curation Expert Panel	RCV003448650	SCV004176271	pathogenic	Hereditary thrombocytopenia and hematologic cancer predisposition syndrome	2024-03-26	reviewed by expert panel	curation	This variant is a frameshift variant resulting in exon deletion (PVS1). This variant is completely absent from population databases with at least 20x coverage for RUNX1 (PM2_supporting). This variant is a nonsense/frameshift variants that is downstream of c.98 (PM5_Supporting). In summary, this variant meets criteria to be classified as likely pathogenic. ACMG/AMP criteria applied, as specified by the Myeloid Malignancy Variant Curation Expert Panel for RUNX1: PVS1, PM2_supporting, PM5_supporting.
ClinGen Monogenic Diabetes Variant Curation Expert Panel	RCV003494034	SCV004242374	uncertain significance	Monogenic diabetes	2024-01-28	reviewed by expert panel	curation	The c.-183T>C variant in the hepatic nuclear factor 4-alpha gene, HNF4A, is a single nucleotide variant in the promoter region of NM_175914.5. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant was identified in 2 unrelated individuals with non-autoimmune and non-absolute/near-absolute insulin-deficient diabetes; however, PS4_Moderate cannot be applied because this number is below the ClinGen MDEP threshold (internal lab contributors). One of these individuals had a clinical history highly specific for HNF4A-monogenic diabetes (MODY probability calculator result >50%, negative genetic testing for HNF1A) (PP4; internal lab contributors). This variant segregated with diabetes with 1 informative meiosis in a single family; however, this does not meet the thresholds for PP1 set by the ClinGen MDEP (internal lab contributors). In summary, c.-183T>C meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 2.0.0, approved 10/11/2023): PP4, PM2_Supporting.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000029934	SCV000052589	likely pathogenic	Maturity-onset diabetes of the young type 2	2011-08-18	criteria provided, single submitter	curation	Converted during submission to Likely pathogenic.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000171455	SCV000221654	likely pathogenic	not provided		criteria provided, single submitter	research
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000171473	SCV000221672	likely pathogenic	not provided		criteria provided, single submitter	research
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000171474	SCV000221673	likely pathogenic	not provided		criteria provided, single submitter	research
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000171479	SCV000221678	likely pathogenic	not provided		criteria provided, single submitter	research
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000171483	SCV000221682	likely pathogenic	not provided		criteria provided, single submitter	research
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000171488	SCV000221687	likely pathogenic	not provided		criteria provided, single submitter	research
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000171489	SCV000221688	likely pathogenic	not provided		criteria provided, single submitter	research
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000171500	SCV000221699	likely pathogenic	not provided		criteria provided, single submitter	research
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000171506	SCV000221705	likely pathogenic	not provided		criteria provided, single submitter	research
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000171508	SCV000221707	likely pathogenic	not provided		criteria provided, single submitter	research
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000171511	SCV000221710	likely pathogenic	not provided		criteria provided, single submitter	research
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000171535	SCV000221734	likely pathogenic	not provided		criteria provided, single submitter	research
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000171536	SCV000221735	likely pathogenic	not provided		criteria provided, single submitter	research
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000171540	SCV000221739	likely pathogenic	not provided		criteria provided, single submitter	research
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000171541	SCV000221740	likely pathogenic	not provided		criteria provided, single submitter	research
Eurofins Ntd Llc (ga)	RCV000178410	SCV000230484	uncertain significance	not provided	2014-10-03	criteria provided, single submitter	clinical testing
Dobyns Lab, Seattle Children's Research Institute	RCV000191932	SCV000246158	pathogenic	Ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome	2014-11-25	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000210429	SCV000256763	pathogenic	Immunodeficiency 104	2014-07-16	criteria provided, single submitter	research	segregates with the phenotype in an affected family
Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust	RCV000210049	SCV000257461	pathogenic	Combined immunodeficiency due to DOCK8 deficiency	2015-08-25	criteria provided, single submitter	clinical testing
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203452	SCV000258328	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203475	SCV000258329	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203458	SCV000258331	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203474	SCV000258332	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203463	SCV000258334	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203486	SCV000258335	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203462	SCV000258337	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203484	SCV000258338	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203447	SCV000258339	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203468	SCV000258340	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203483	SCV000258341	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203451	SCV000258342	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203466	SCV000258343	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203489	SCV000258344	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203456	SCV000258345	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203472	SCV000258346	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203499	SCV000258350	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203453	SCV000258351	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203481	SCV000258355	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203495	SCV000258356	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203464	SCV000258357	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203480	SCV000258358	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203449	SCV000258359	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203485	SCV000258361	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203448	SCV000258362	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203469	SCV000258363	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203491	SCV000258364	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203459	SCV000258365	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203467	SCV000258366	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203490	SCV000258367	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203473	SCV000258369	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203488	SCV000258370	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203492	SCV000258373	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203498	SCV000258376	pathogenic	Hereditary spastic paraplegia 4	2014-08-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203289	SCV000258388	likely pathogenic	Bosch-Boonstra-Schaaf optic atrophy syndrome	2014-02-06	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000203294	SCV000258389	likely pathogenic	Bosch-Boonstra-Schaaf optic atrophy syndrome	2014-02-06	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000210394	SCV000258457	pathogenic	Chromosome 17p13.1 deletion syndrome	2015-11-06	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000210404	SCV000258458	pathogenic	Chromosome 17p13.1 deletion syndrome	2015-11-06	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000210387	SCV000258459	pathogenic	Chromosome 17p13.1 deletion syndrome	2015-11-06	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000210397	SCV000258460	pathogenic	Chromosome 17p13.1 deletion syndrome	2015-11-06	criteria provided, single submitter	research
Elsea Laboratory, Baylor College of Medicine	RCV000455872	SCV000264470	pathogenic	MBD5 associated neurodevelopmental disorder	2012-10-01	criteria provided, single submitter	research
Elsea Laboratory, Baylor College of Medicine	RCV000454803	SCV000264471	pathogenic	MBD5 associated neurodevelopmental disorder	2012-10-01	criteria provided, single submitter	research
Elsea Laboratory, Baylor College of Medicine	RCV000455222	SCV000264472	pathogenic	MBD5 associated neurodevelopmental disorder	2012-10-01	criteria provided, single submitter	research
Elsea Laboratory, Baylor College of Medicine	RCV000455812	SCV000264473	pathogenic	MBD5 associated neurodevelopmental disorder	2012-10-01	criteria provided, single submitter	research
Elsea Laboratory, Baylor College of Medicine	RCV000454759	SCV000264474	pathogenic	MBD5 associated neurodevelopmental disorder	2012-10-01	criteria provided, single submitter	research
Elsea Laboratory, Baylor College of Medicine	RCV000477897	SCV000264477	pathogenic	MBD5 associated neurodevelopmental disorder	2012-10-01	criteria provided, single submitter	research
Elsea Laboratory, Baylor College of Medicine	RCV000454618	SCV000264478	pathogenic	MBD5 associated neurodevelopmental disorder	2012-10-01	criteria provided, single submitter	research
Elsea Laboratory, Baylor College of Medicine	RCV000477751	SCV000264479	pathogenic	MBD5 associated neurodevelopmental disorder	2012-10-01	criteria provided, single submitter	research
Elsea Laboratory, Baylor College of Medicine	RCV000455254	SCV000264480	pathogenic	MBD5 associated neurodevelopmental disorder	2012-10-01	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000210384	SCV000266398	pathogenic	Immunodeficiency 23	2014-07-03	criteria provided, single submitter	research	segregates with the phenotype in an affected family
Baylor-Hopkins Center for Mendelian Genomics, Johns Hopkins University School of Medicine	RCV000210452	SCV000266536	pathogenic	Loeys-Dietz syndrome 4		criteria provided, single submitter	research
Baylor-Hopkins Center for Mendelian Genomics, Johns Hopkins University School of Medicine	RCV000210464	SCV000266537	pathogenic	Loeys-Dietz syndrome 4		criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000488894	SCV000267603	pathogenic	not provided	2016-04-26	criteria provided, single submitter	research	compound heterozygous deletion identified in patient with congenital cataract, seizures, cerebellar and brainstem hypoplasia
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000488906	SCV000267604	pathogenic	not provided	2016-04-26	criteria provided, single submitter	research	compound heterozygous deletion identified in patient with congenital cataract, seizures, cerebellar and brainstem hypoplasia
Geschwind lab, University of California Los Angeles	RCV000225569	SCV000282087	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225670	SCV000282088	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225439	SCV000282089	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225548	SCV000282090	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225681	SCV000282091	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225457	SCV000282092	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225542	SCV000282093	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225679	SCV000282094	likely pathogenic	Autism spectrum disorder		criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225451	SCV000282095	likely pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225595	SCV000282096	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225368	SCV000282097	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225469	SCV000282098	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225572	SCV000282099	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225402	SCV000282100	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225508	SCV000282101	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225645	SCV000282102	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225379	SCV000282103	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225522	SCV000282104	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225625	SCV000282105	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research	The CNV is pathogenic but didn’t cause the disorder in this individual due to incomplete penetrance.
Geschwind lab, University of California Los Angeles	RCV000225436	SCV000282106	likely pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225546	SCV000282107	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225619	SCV000282108	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225434	SCV000282109	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225539	SCV000282110	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225676	SCV000282111	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225448	SCV000282112	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225559	SCV000282113	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225649	SCV000282114	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225471	SCV000282115	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225587	SCV000282116	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225404	SCV000282117	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225463	SCV000282118	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225607	SCV000282119	association	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225377	SCV000282120	association	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225525	SCV000282121	association	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225621	SCV000282122	association	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225398	SCV000282123	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225516	SCV000282124	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225620	SCV000282125	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225430	SCV000282126	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225540	SCV000282127	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225633	SCV000282128	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225410	SCV000282129	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225556	SCV000282130	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225671	SCV000282131	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225446	SCV000282132	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225549	SCV000282133	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225687	SCV000282134	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225459	SCV000282135	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225604	SCV000282136	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225659	SCV000282137	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research	The CNV is pathogenic but didn’t cause the disorder in this individual due to incomplete penetrance.
Geschwind lab, University of California Los Angeles	RCV000225479	SCV000282138	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225596	SCV000282139	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225373	SCV000282140	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225512	SCV000282141	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225576	SCV000282142	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225386	SCV000282143	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225492	SCV000282144	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225630	SCV000282145	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225408	SCV000282146	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research	The CNV is pathogenic but didn’t cause the disorder in this individual due to incomplete penetrance.
Geschwind lab, University of California Los Angeles	RCV000225528	SCV000282147	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research	The CNV is pathogenic but didn’t cause the disorder in this individual due to incomplete penetrance.
Geschwind lab, University of California Los Angeles	RCV000225629	SCV000282148	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225442	SCV000282149	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225550	SCV000282150	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225685	SCV000282151	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225421	SCV000282158	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225563	SCV000282159	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225663	SCV000282160	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225455	SCV000282161	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225599	SCV000282162	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225655	SCV000282163	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225476	SCV000282164	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225574	SCV000282165	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225391	SCV000282166	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225489	SCV000282167	likely pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225609	SCV000282168	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225382	SCV000282169	pathogenic	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225526	SCV000282170	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225626	SCV000282171	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225438	SCV000282172	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225497	SCV000282173	association	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225644	SCV000282174	association	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225420	SCV000282175	association	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225541	SCV000282176	association	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225635	SCV000282177	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225416	SCV000282178	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225562	SCV000282179	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225652	SCV000282180	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225468	SCV000282181	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225537	SCV000282182	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225674	SCV000282183	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225465	SCV000282184	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225606	SCV000282185	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225383	SCV000282186	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Geschwind lab, University of California Los Angeles	RCV000225486	SCV000282187	uncertain significance	Autism spectrum disorder	2015-10-12	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000234859	SCV000291989	pathogenic	Syndromic X-linked intellectual disability Lubs type	2015-03-13	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000234878	SCV000291990	pathogenic	Syndromic X-linked intellectual disability Lubs type	2015-03-13	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000234882	SCV000291993	pathogenic	Blepharophimosis; Absent speech; Thick lower lip vermilion; Thin upper lip vermilion; Long eyelashes; Intellectual disability, moderate	2014-03-27	criteria provided, single submitter	clinical testing
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000235056	SCV000292303	pathogenic	Spondylocostal dysostosis 5	2015-11-15	criteria provided, single submitter	research	This variant was observed in 17 individuals with vertebral malformations and rib abnormalities. In each case it was found to be in trans with a high-risk TBX6 haplotype, T-C-A (rs2289292, rs3809624, rs3809627).
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000235073	SCV000292310	likely pathogenic	Epilepsy, progressive myoclonic, 1B	2015-09-17	criteria provided, single submitter	research	This deletion was identified in a patient with seizures and neuropathy. There was no evidence of the deletion in parental samples, indicating that the CNV likely arose de novo in the patient. There are reports in the literature of heterozygous mutations in PRICKLE1 in patients with seizures (PMID: 21276947). The patient also has a de novo heterozygous variant in MFN2.
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000235046	SCV000292314	uncertain significance	Peripheral neuropathy	2015-09-17	criteria provided, single submitter	research	This deletion was identified in an individual with peripheral neuropathy. There is no association in the literature between KIF24 and neuropathy. This individual also has an MFN2 pathogenic variant.
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000235057	SCV000292315	likely pathogenic	Charcot-Marie-Tooth disease type 1B	2015-09-17	criteria provided, single submitter	research	This deletion was identified in an individual with peripheral neuropathy.
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000235080	SCV000292316	pathogenic	Smith-Magenis syndrome	2015-11-12	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000235042	SCV000292317	pathogenic	Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2	2015-11-12	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000235066	SCV000292340	pathogenic	X-linked acrogigantism due to Xq26 microduplication	2015-11-12	criteria provided, single submitter	research	XLAG is a newly described condition, which is rare and the phenotype is incompletely characterized, particularly in terms of clinical responses to treatment. The aim of this study was to clinically characterize X-LAG in an expanded cohort of 18 affected patients.
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000235052	SCV000292363	pathogenic	PHARC syndrome	2015-08-18	criteria provided, single submitter	research	This copy number variation has been previously reported as disease-causing and was identified in a family with PHARC.
Eurofins Ntd Llc (ga)	RCV000385479	SCV000330986	likely benign	not specified	2015-09-29	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000299568	SCV000331783	uncertain significance	not provided	2016-01-28	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000318149	SCV000334678	uncertain significance	not provided	2015-08-27	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000273531	SCV000335444	uncertain significance	not provided	2015-09-15	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000337319	SCV000336997	likely pathogenic	not provided	2015-10-26	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000400412	SCV000340516	pathogenic	not provided	2016-03-18	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000349357	SCV000340741	uncertain significance	not provided	2016-04-15	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000309059	SCV000340769	likely benign	not specified	2016-04-03	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000299738	SCV000341602	uncertain significance	not provided	2016-05-09	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000308584	SCV000341702	uncertain significance	not provided	2016-05-18	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000315072	SCV000341808	uncertain significance	not provided	2016-06-07	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000278127	SCV000341988	uncertain significance	not provided	2016-05-10	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000340414	SCV000343758	uncertain significance	not provided	2016-07-12	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000292125	SCV000344235	benign	not specified	2016-08-08	criteria provided, single submitter	clinical testing
Robarts Research Institute, Western University	RCV000408813	SCV000484813	likely pathogenic	Hypercholesterolemia, familial, 1		criteria provided, single submitter	clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000414385	SCV000490158	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000413848	SCV000490160	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000414056	SCV000490166	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000414007	SCV000490172	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000413482	SCV000490174	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000414360	SCV000490175	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2015-10-02	criteria provided, single submitter	clinical testing
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000415472	SCV000493131	likely pathogenic	X-linked acrogigantism due to Xq26 microduplication	2016-01-01	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000415468	SCV000493132	likely pathogenic	X-linked acrogigantism due to Xq26 microduplication	2016-01-01	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000415470	SCV000493133	likely pathogenic	X-linked acrogigantism due to Xq26 microduplication	2016-01-01	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000415471	SCV000493134	likely pathogenic	X-linked acrogigantism due to Xq26 microduplication	2016-01-01	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000520873	SCV000494285	pathogenic	Prader-Willi syndrome		criteria provided, single submitter	research	This deletion of 15q11q13 is de novo and represents the typical recurrent type 2 deletion.
Neurogenetics Laboratory - MEYER, AOU Meyer	RCV000416971	SCV000494569	pathogenic	Epileptic encephalopathy	2016-11-16	criteria provided, single submitter	clinical testing
Knight Diagnostic Laboratories, Oregon Health and Sciences University	RCV000454279	SCV000538074	pathogenic	Hypoparathyroidism-retardation-dysmorphism syndrome	2016-04-08	criteria provided, single submitter	clinical testing	The heterozygous deletion of exons 3 and 4 that was detected by a single copy loss of 16 oligonucleotide probes spanning approximately 7,842 bp in the TBCE gene, Hg19 chr1: g.(235575072_235577473)_(235582954_235583424)del (NM_ 003193) has not been previously reported in an affected individual. TBCE is the only gene implicated in HRD and suggests that this disorder has a single gene etiology. The out-of-frame deletion leads to premature protein truncation. Deletions and truncation variants are common mechanisms of disease; the c.155-166del12 in the TBCE gene is considered the most common pathogenic variant for this condition (Kerkeni E et al., 2015). Based on these criteria, this CNV is interpreted at pathogenic. We have confirmed the findings using a custom exon-centric microarray.
Knight Diagnostic Laboratories, Oregon Health and Sciences University	RCV000454326	SCV000538075	likely pathogenic	Infantile nephronophthisis	2016-04-19	criteria provided, single submitter	clinical testing	A heterozygous deletion of the 5â€™-UTR and exons 1 and 2 was detected by a single copy loss of 117 oligonucleotide probes spanning approximately 139,883 bp in the INVS gene, Hg19 chr9: g.( 102814578_102860399)_(102967421_102968415)del (NM_ 001318381). This variant has not been previously reported in an affected individual. Exon 2, which is deleted in this CNV, contains the start codon, implying a loss of the initiation codon. Several frameshift and nonsense variants in this gene have been described in affected individuals (Tory K et al., 2009) suggesting that loss of functions is mechanism of disease. Based on these criteria, this CNV is interpreted at Likely Pathogenic. We have confirmed the findings using a custom exon-centric microarray.
Knight Diagnostic Laboratories, Oregon Health and Sciences University	RCV000454211	SCV000538076	likely pathogenic	Fanconi anemia complementation group A	2016-04-01	criteria provided, single submitter	clinical testing	The c.1627-?_2778+?del deletion in the FANCA gene is novel, however, similar sized deletions in the same genomic vicinity have been previously reported as pathogenic (deletion of exons 18-25: Moghrabi et al. 2009) (deletion of exons 21-29: Castella et al., 2011). Mutations in the coding region of FANCA account for approximately 60-70% of Fanconi Anemia Complementation Group A (FA-A) patients, and approximately 10% of pathogenic mutations are large, multi-exonic deletions (Castella et al., 2011). This deletion encompasses amino acids 543-926 in the FANCA protein, and removes a portion of the BRCA-interacting region (amino acids 740-1083) as well as three important phosphoserines (amino acids 849, 850 and 858) (Folias et al., 2002). In addition, this deletion also disrupts a known nuclear export sequence (amino acids 860-880), which would effectively abolish protein transport from the nucleus to the cytoplasm (Ferrer et al., 2005). Therefore, this novel 11-exon deletion is expected to severely truncate the FANCA protein and compromise its function. The collective evidence supports the classification of the c.1627-?_2778+?del as a recessive likely pathogenic variant for Fanconi Anemia, Complementation Group A.
Knight Diagnostic Laboratories, Oregon Health and Sciences University	RCV000454303	SCV000538077	likely pathogenic	Fanconi anemia complementation group A	2016-04-01	criteria provided, single submitter	clinical testing	The c.1627-?_2778+?del deletion in the FANCA gene is novel, however, similar sized deletions in the same genomic vicinity have been previously reported as pathogenic (deletion of exons 18-25: Moghrabi et al. 2009) (deletion of exons 21-29: Castella et al., 2011). Mutations in the coding region of FANCA account for approximately 60-70% of Fanconi Anemia Complementation Group A (FA-A) patients, and approximately 10% of pathogenic mutations are large, multi-exonic deletions (Castella et al., 2011). This deletion encompasses amino acids 543-926 in the FANCA protein, and removes a portion of the BRCA-interacting region (amino acids 740-1083) as well as three important phosphoserines (amino acids 849, 850 and 858) (Folias et al., 2002). In addition, this deletion also disrupts a known nuclear export sequence (amino acids 860-880), which would effectively abolish protein transport from the nucleus to the cytoplasm (Ferrer et al., 2005). Therefore, this novel 11-exon deletion is expected to severely truncate the FANCA protein and compromise its function. The collective evidence supports the classification of the c.1627-?_2778+?del as a recessive likely pathogenic variant for Fanconi Anemia, Complementation Group A.
Herman Laboratory, Nationwide Children's Hospital	RCV000490618	SCV000579289	pathogenic	PTEN hamartoma tumor syndrome	2017-03-01	criteria provided, single submitter	clinical testing
Yang An-Suei Laboratory, Academia Sinica	RCV000504607	SCV000583426	pathogenic	Breast neoplasm		criteria provided, single submitter	clinical testing
Counsyl	RCV000499484	SCV000590824	pathogenic	alpha Thalassemia	2015-01-14	criteria provided, single submitter	clinical testing	-Î±3.7 is classified as an alpha+ mutation.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000500763	SCV000590971	pathogenic	Hereditary breast ovarian cancer syndrome	2012-07-10	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000502731	SCV000590975	uncertain significance	not specified		criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000500209	SCV000590979	pathogenic	Hereditary breast ovarian cancer syndrome	2016-10-14	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000504485	SCV000590987	pathogenic	Lynch syndrome	2016-02-05	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000503082	SCV000590992	pathogenic	Lynch syndrome		criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000499720	SCV000590993	pathogenic	Lynch syndrome		criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000499564	SCV000590996	pathogenic	Lynch syndrome		criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000501388	SCV000590997	pathogenic	Lynch syndrome	2015-05-20	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000503363	SCV000591001	pathogenic	Lynch syndrome		criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000500604	SCV000591002	pathogenic	Lynch syndrome	2014-01-30	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000502402	SCV000591003	pathogenic	Lynch syndrome	2013-01-18	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000504163	SCV000591004	likely pathogenic	Lynch syndrome	2016-08-05	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000500987	SCV000591008	pathogenic	Autosomal recessive polycystic kidney disease	2016-07-27	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000504539	SCV000591010	pathogenic	Autosomal recessive polycystic kidney disease	2016-07-29	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000500855	SCV000591011	likely pathogenic	Lynch syndrome	2014-12-11	criteria provided, single submitter	clinical testing
Center of Genomic medicine, Geneva, University Hospital of Geneva	RCV000500418	SCV000598154	pathogenic	Telangiectasia, hereditary hemorrhagic, type 1	2016-08-04	criteria provided, single submitter	clinical testing
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000505253	SCV000599309	pathogenic	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	curation
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000505214	SCV000599316	pathogenic	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	curation
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000505243	SCV000599317	pathogenic	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	curation
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000505182	SCV000599318	pathogenic	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	curation
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000505219	SCV000599319	uncertain significance	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	curation
Cardiovascular Research Group, Instituto Nacional de Saude Doutor Ricardo Jorge	RCV000505246	SCV000599320	uncertain significance	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	curation
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000505401	SCV000599662	pathogenic	Familial X-linked hypophosphatemic vitamin D refractory rickets	2013-11-06	criteria provided, single submitter	clinical testing
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000505435	SCV000599703	pathogenic	Familial X-linked hypophosphatemic vitamin D refractory rickets	2017-08-31	criteria provided, single submitter	clinical testing
Department of Medical Genetics, Oslo University Hospital	RCV000506461	SCV000605722	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2016-01-25	criteria provided, single submitter	clinical testing	Heterozygous deletion of exon 10 (also known as exon 11)
Fundacion Hipercolesterolemia Familiar	RCV000509444	SCV000607397	uncertain significance	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research
Fundacion Hipercolesterolemia Familiar	RCV000509098	SCV000607398	uncertain significance	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research
Fundacion Hipercolesterolemia Familiar	RCV000509204	SCV000607427	uncertain significance	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research
Fundacion Hipercolesterolemia Familiar	RCV000509145	SCV000607447	uncertain significance	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research
Fundacion Hipercolesterolemia Familiar	RCV000509345	SCV000607700	uncertain significance	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research
Fundacion Hipercolesterolemia Familiar	RCV000509291	SCV000607711	uncertain significance	Hypercholesterolemia, familial, 1	2016-03-01	criteria provided, single submitter	research
Labcorp Genetics (formerly Invitae), Labcorp	RCV000548818	SCV000623513	uncertain significance	Hypertrophic cardiomyopathy	2018-06-28	criteria provided, single submitter	clinical testing	A gross duplication of the genomic region encompassing the full coding sequence of the TNNI3 gene has been identified. The boundaries of this event are unknown as the duplication extends beyond the assayed region for this gene and therefore may encompass additional genes. As the precise location of this duplication is unknown, it may be in tandem or it may be located elsewhere in the genome. This variant has not been reported in the literature in individuals with a TNNI3-related disease. In summary, the exact genomic location of this variant is unknown and the effect of this whole TNNI3 gene duplication is unknown. Therefore, it has been classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000531596	SCV000624563	uncertain significance	Hereditary nonpolyposis colorectal neoplasms	2017-04-11	criteria provided, single submitter	clinical testing	This variant is a gross duplication of the genomic region encompassing exons 1-4 of the MSH2 gene. If EPCAM has been tested and no copy number events are reported for it, then the 5' boundary of this event lies between the EPCAM and MSH2 genes. If EPCAM has not been tested, the 5' end of this event is unknown as it extends beyond the assayed region of this test. The 3' boundary is likely confined to intron 4 of the MSH2 gene. This duplication has not been reported in the literature in individuals with an MSH2-related disease. In summary, the exact genomic location of this variant is unknown and the impact of this duplication on MSH2 protein function has not been established. Therefore, it has been classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000544514	SCV000624570	likely pathogenic	Hereditary nonpolyposis colorectal neoplasms	2018-03-29	criteria provided, single submitter	clinical testing	This variant results in a copy number gain of the genomic region encompassing exons 5-7 of the MSH2 gene.Â¬â€ While the exact position of this variant cannot be determined from this data, sub-genic copy number gains are generally in tandem (PMID: 25640679) and may result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with MSH2-related disease.Â¬â€ ClinVar contains an entry for MSH2 duplications of exons 5-7 (Variation ID:Â¬â€ 218047). Loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000542078	SCV000624598	uncertain significance	Hereditary nonpolyposis colorectal neoplasms	2017-02-13	criteria provided, single submitter	clinical testing	This variant is a gross duplication of the genomic region encompassing exons 6-14 of the PMS2 gene. While the exact position of the duplicated exons cannot be determined from this data, the duplicated copy of this region is likely in tandem and in-frame, therefore preserving the integrity of the reading frame. This variant has not been reported in the literature in individuals with a PMS2-related disease. In summary, the exact genomic location of this variant is unknown and the impact of this duplication on PMS2 protein function has not been established. Therefore, it has been classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000546533	SCV000626134	uncertain significance	Fanconi anemia	2017-06-23	criteria provided, single submitter	clinical testing	A gross duplication of the genomic region encompassing the full coding sequence of the FANCG gene has been identified. The boundaries of this event are unknown as the duplication extends beyond the assayed region for this gene and therefore may encompass additional genes. As the precise location of this duplication is unknown, it may be in tandem or it may be located elsewhere in the genome. This variant has not been reported in the literature in individuals with a FANCG-related disease. The exact genomic location of this variant is unknown. In summary, this variant has uncertain impact on FANCG function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000557921	SCV000629385	uncertain significance	Spastic paraplegia	2017-03-21	criteria provided, single submitter	clinical testing	A gross duplication of the genomic region encompassing the full coding sequence of the HSPD1 gene has been identified. The boundaries of this event are unknown as the duplication extends beyond the assayed region for this gene and therefore may encompass additional genes. As the precise location of this duplication is unknown, it may be in tandem or it may be located elsewhere in the genome. This variant has not been reported in the literature in individuals with a HSPD1-related disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the duplicated amino acids is currently unknown. In summary, the exact genomic location of this variant is unknown and the impact of this duplication on HSPD1 protein function has not been established. Therefore, it has been classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000550770	SCV000630741	uncertain significance	Hereditary pancreatitis	2017-07-07	criteria provided, single submitter	clinical testing	A gross duplication of the genomic region encompassing the full coding sequence of the SPINK1 gene has been identified. The boundaries of this event are unknown as the duplication extends beyond the assayed region for this gene and therefore may encompass additional genes. As the precise location of this duplication is unknown, it may be in tandem or it may be located elsewhere in the genome. This variant has not been reported in the literature in individuals with SPINK1-related disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000554640	SCV000631437	uncertain significance	Ehlers-Danlos syndrome, classic type	2017-02-12	criteria provided, single submitter	clinical testing	This variant is a gross duplication of the genomic region encompassing exons 8-54 of the COL5A2 gene. The 5' boundary is likely confined to intron 7. The 3' end of this event is unknown as it extends beyond the assayed region for this gene and therefore may encompass additional genes . As the precise location of this duplication is unknown, it may be in tandem or it may be located elsewhere in the genome. Duplications of exons 8-54 Â¬â€ sequence have not been reported in the literature in individuals with a COL5A2-related disease. In summary, the exact genomic location of this variant is unknown and the impact of this duplication on COL5A2 protein function has not been established. Therefore, it has been classified as a Variant of Unknown Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000527946	SCV000632906	likely pathogenic	Familial cancer of breast	2017-11-03	criteria provided, single submitter	clinical testing	This variant is a gross duplication of the genomic region encompassing exons 2-3 of the BARD1 gene. While the exact position of the duplicated exons cannot be determined from this data, sub-genic duplications are generally in tandem (PMID: 25640679) and may result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with BARD1-related disease. Loss-of-function variants in BARD1 are known to be pathogenic (PMID: 20077502, 21344236). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000557636	SCV000635101	likely pathogenic	Hereditary breast ovarian cancer syndrome	2017-03-21	criteria provided, single submitter	clinical testing	This variant is a gross duplication of the genomic region encompassing exons 12-13 of the BRCA2 gene. While the exact position of the duplicated exons cannot be determined from this data, the duplicated copy of this region is likely in tandem and may result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). In summary, sub-genic duplications are generally in tandem (PMID: 25640679), and result in an absent or disrupted protein. However, the exact location of this duplication has not been confirmed. Therefore, it has been classified as Likely Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000545391	SCV000636113	benign	Nephronophthisis	2017-02-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000534213	SCV000638448	uncertain significance	Neuronopathy, distal hereditary motor, type 7A; Congenital myasthenic syndrome 20	2017-07-05	criteria provided, single submitter	clinical testing	A gross duplication of the genomic region encompassing the full coding sequence of the SLC5A7 gene has been identified. The boundaries of this event are unknown as the duplication extends beyond the assayed region for this gene and therefore may encompass additional genes. As the precise location of this duplication is unknown, it may be in tandem or it may be located elsewhere in the genome. This duplication has not been reported in the literature in individuals with SLC5A7-related disease. Experimental studies are not available for this duplication and the functional significance of an additional copy of this gene is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000528877	SCV000638530	uncertain significance	Hereditary spastic paraplegia 30; Neuropathy, hereditary sensory, type 2C; Intellectual disability, autosomal dominant 9	2016-09-23	criteria provided, single submitter	clinical testing	This variant is a gross duplication of the genomic region encompassing exons 38 to 46 of the KIF1A gene. The 5' boundary is likely confined to intron 37. The 3' end of this event is unknown as it extends beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals with a KIF1A-related disease, and its frequency in the general population is not known. In summary, because the exact 3' boundary of this variant has not been determined, and whether this duplication occurs in tandem is not known, the impact of this duplication on KIF1A protein function can not be established. Therefore, it has been classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000534639	SCV000638531	benign	Hereditary spastic paraplegia 30; Neuropathy, hereditary sensory, type 2C; Intellectual disability, autosomal dominant 9	2018-01-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000543941	SCV000646080	uncertain significance	Progressive familial heart block type IB	2018-01-04	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000534711	SCV000647150	likely pathogenic	Familial adenomatous polyposis 1	2017-02-17	criteria provided, single submitter	clinical testing	This variant is a gross duplication of the genomic region encompassing exons 2-4 of the APC gene. The 5' end of this event is likely confined to intron 1 of the APC gene. The 3' boundary is likely confined to intron 4 of the APC gene. While the exact position of the duplicated exons cannot be determined from this data, the duplicated copy of this region is likely in tandem and may result in an absent or disrupted protein product. While this particular duplication has not been reported in the literature, loss-of-function variants including gross alterations in APC are known to be pathogenic (PMID: 23159591). In summary, sub-genic duplications are generally in tandem (PMID: 25640679), and result in an absent or disrupted protein. However, the exact location of this duplication has not been confirmed. Therefore, it has been classified as Likely Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000548052	SCV000648588	uncertain significance	Neuroblastoma, susceptibility to, 3	2017-04-10	criteria provided, single submitter	clinical testing	This variant is a gross duplication of the genomic region encompassing exons 5 to 29 of the ALK gene. The 5' boundary is likely confined to intron 4. The 3' end of this event is unknown as it extends beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals with an ALK-related disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the duplicated amino acids is currently unknown. In summary, the exact genomic location of this variant is unknown and the impact of this duplication on ALK protein function has not been established. Therefore, it has been classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000547325	SCV000650689	uncertain significance	Interstitial lung disease 2; Dyskeratosis congenita, autosomal dominant 2	2017-03-30	criteria provided, single submitter	clinical testing	This variant is a gross duplication of the genomic region encompassing exons 7-16 of the TERT gene. The 5' boundary is likely confined to intron 6. The 3' end of this event is unknown as it extends beyond the assayed region for this gene and therefore may encompass additional genes. This gross duplication has not been reported in the literature in an individual with TERT-related disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the duplicated amino acids is currently unknown. In summary, the exact genomic location of this variant is unknown and the impact of this duplication on TERT protein function has not been established. Therefore, it has been classified as a Variant of Uncertain Significance
Labcorp Genetics (formerly Invitae), Labcorp	RCV000527830	SCV000650882	uncertain significance	Myofibrillar myopathy 5; Distal myopathy with posterior leg and anterior hand involvement; Hypertrophic cardiomyopathy 26; Dilated Cardiomyopathy, Dominant	2017-01-24	criteria provided, single submitter	clinical testing	This variant is a gross duplication of the genomic region encompassing exon 47 of the FLNC gene. While the exact position of the duplicated exon cannot be determined from this data, the duplicated copy of this region is likely in tandem and in-frame, therefore preserving the integrity of the reading frame. This variant has not been reported in the literature in an individual with a FLNC-related disease. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the duplicated amino acids is currently unknown. In summary, the exact genomic location of this variant is unknown and the impact of this duplication on FLNC protein function has not been established. Therefore, it has been classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000552282	SCV000652857	uncertain significance	Joubert syndrome 20; Meckel syndrome, type 11	2017-06-07	criteria provided, single submitter	clinical testing	This variant is a gross duplication of the genomic region encompassing exons 4-6 of the TMEM231 gene. The 5' boundary is likely confined to intron 3. The 3' end of this event is unknown as it extends beyond the assayed region for this gene and therefore may encompass additional genes. The exact genomic location of this variant is unknown. Gross duplications have not been reported in the literature in individuals with a TMEM231-related disease. In summary, this variant has uncertain impact on TMEM231 function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000558514	SCV000658808	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2018-01-19	criteria provided, single submitter	clinical testing	This variant is a gross duplication of the genomic region encompassing exons 6-9 of the SMAD3 gene. The 5' boundary is likely confined to intron 5. The 3' end of this event is unknown as it extends beyond the assayed region for this gene and therefore may encompass additional genes. This variant has not been reported in the literature in individuals with SMAD3-related disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000677251	SCV000681429	pathogenic	Optic nerve hypoplasia		criteria provided, single submitter	research	SOX5 previously described in Lamb-Schaffer syndrome that sometimes involves optic nerve hypoplasia. This individual also has intellectual disability and heart defects, also reported in Lamb-Schaffer syndrome. Similar deletions of SOX5 causing the same phenotype have been reported, PMID 22290657.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000585924	SCV000693907	pathogenic	Glycogen storage disease, type II	2017-06-25	criteria provided, single submitter	research	PVS1: Identified truncating variant in compound heterozygote with common promoter pathogenic variant. Previously reported in 2 patients in the literature with adult onset GSDII. PM2: Absent from gnomAD (well covered) and PM3: 3 compound heterozygotes with GSDII, including 2 in literature (PMID: 17616415).
Eurofins Ntd Llc (ga)	RCV000594755	SCV000703106	uncertain significance	not provided	2017-02-27	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000592422	SCV000703422	uncertain significance	not provided	2017-01-09	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000593500	SCV000704742	uncertain significance	not provided	2017-01-06	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000597577	SCV000706542	uncertain significance	not provided	2017-02-27	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000597921	SCV000707424	uncertain significance	not provided	2017-03-30	criteria provided, single submitter	clinical testing
Center For Human Genetics And Laboratory Diagnostics, Dr. Klein, Dr. Rost And Colleagues	RCV000624863	SCV000740317	pathogenic	Hereditary spherocytosis type 2	2018-03-29	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000627115	SCV000747919	likely pathogenic	Autistic behavior; Severe global developmental delay	2012-12-17	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000627116	SCV000747920	likely pathogenic	Autistic behavior; Severe global developmental delay	2017-04-30	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000627117	SCV000747921	likely pathogenic	Autistic behavior; Moderate global developmental delay	2017-05-27	criteria provided, single submitter	clinical testing
Department of Psychiatry, Nagoya University	RCV000754118	SCV000777921	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754119	SCV000777922	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754124	SCV000777927	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754129	SCV000777932	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754131	SCV000777934	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754132	SCV000777935	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754147	SCV000777950	pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754155	SCV000777958	pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754156	SCV000777959	pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754157	SCV000777960	pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754158	SCV000777961	likely pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754160	SCV000777963	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754162	SCV000777965	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754164	SCV000777967	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754166	SCV000777969	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754167	SCV000777970	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754168	SCV000777971	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754171	SCV000777974	pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754172	SCV000777975	pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754173	SCV000777976	pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754174	SCV000777977	pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754175	SCV000777978	pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754177	SCV000777980	pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754179	SCV000777982	likely pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754180	SCV000777983	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754182	SCV000777985	pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754184	SCV000777987	pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754185	SCV000777988	pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754186	SCV000777989	pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754188	SCV000777991	pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754189	SCV000777992	pathogenic	Autism; Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754201	SCV000778004	pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754205	SCV000778008	likely pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754211	SCV000778014	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754212	SCV000778015	likely pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754229	SCV000778032	likely pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754248	SCV000778051	pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754249	SCV000778052	pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754250	SCV000778053	pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754256	SCV000778059	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754258	SCV000778061	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754259	SCV000778062	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754267	SCV000778070	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754277	SCV000778080	likely pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754283	SCV000778086	likely pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754289	SCV000778092	likely pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754292	SCV000778095	likely pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754324	SCV000778127	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754329	SCV000778132	likely pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754330	SCV000778133	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754331	SCV000778134	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754332	SCV000778135	likely pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754333	SCV000778136	pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754334	SCV000778137	pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754346	SCV000778149	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754347	SCV000778150	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754348	SCV000778151	likely pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754349	SCV000778152	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754350	SCV000778153	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754351	SCV000778154	likely pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754352	SCV000778155	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754353	SCV000778156	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754362	SCV000778165	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754363	SCV000778166	likely pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754364	SCV000778167	likely pathogenic	Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754365	SCV000778168	pathogenic	Autism; Schizophrenia	2018-03-20	criteria provided, single submitter	research
Department of Psychiatry, Nagoya University	RCV000754378	SCV000778181	likely pathogenic	Autism	2018-03-20	criteria provided, single submitter	research
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000754926	SCV000787512	benign	Global developmental delay	2018-05-08	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000754927	SCV000787513	pathogenic	Global developmental delay	2018-05-08	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000754928	SCV000787514	likely benign	Global developmental delay	2018-05-08	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000754929	SCV000787515	benign	not specified	2018-05-08	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000754930	SCV000787516	benign	not specified	2018-05-08	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000754931	SCV000787517	benign	not specified	2018-05-08	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000754932	SCV000787518	benign	not specified	2018-05-08	criteria provided, single submitter	clinical testing
Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano	RCV000754403	SCV000787664	uncertain significance	Primary amenorrhea	2018-06-01	criteria provided, single submitter	research
Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano	RCV000754413	SCV000787674	likely benign	Primary amenorrhea	2018-06-01	criteria provided, single submitter	research
Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano	RCV000754448	SCV000787709	likely benign	Primary amenorrhea	2018-06-01	criteria provided, single submitter	research
Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano	RCV000754469	SCV000787730	uncertain significance	Primary amenorrhea	2018-06-01	criteria provided, single submitter	research
Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano	RCV000754473	SCV000787734	likely benign	Primary amenorrhea	2018-06-01	criteria provided, single submitter	research
Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano	RCV000754474	SCV000787735	uncertain significance	Primary amenorrhea	2018-06-01	criteria provided, single submitter	research
Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano	RCV000754479	SCV000787740	uncertain significance	Primary amenorrhea	2018-06-01	criteria provided, single submitter	research
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000754946	SCV000788371	pathogenic	Jeune thoracic dystrophy	2018-05-01	criteria provided, single submitter	research
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000754969	SCV000788396	pathogenic	1q24q25 microdeletion syndrome	2018-05-01	criteria provided, single submitter	research
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677147	SCV000803307	uncertain significance	not provided	2018-04-03	criteria provided, single submitter	provider interpretation	This deletion was identified in an 8 year old female with intellectual disability, hyperkinesis, seizure disorder, and feeding disorder. She has a history of congenital hip dysplasia, chronic constipation, atrial septal defect, strabismus, and Raynaud's phenomenon. Brain MRI showed mild diffuse loss of the deep white matter in both cerebral hemispheres. This patient also has a pathogenic 43 Mb duplication at 4q. These copy number variants are a result of a derivative chromosome 4. The patient's sister, who is similarly affected, has the same derivative chromosome 4.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677148	SCV000803308	pathogenic	not provided	2018-04-03	criteria provided, single submitter	provider interpretation	This duplication was identified in an 8 year old female with intellectual disability, hyperkinesis, seizure disorder, and feeding disorder. She has a history of congenital hip dysplasia, chronic constipation, atrial septal defect, strabismus, and Raynaud's phenomenon. Brain MRI showed mild diffuse loss of the deep white matter in both cerebral hemispheres. This patient also has a 770 kilobase deletion at 4pter, which is of uncertain significance. These copy number variants are a result of a derivative chromosome 4. The patient's sister, who is similarly affected, has the same derivative chromosome 4.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677149	SCV000803309	pathogenic	not provided	2018-04-03	criteria provided, single submitter	provider interpretation	This duplication was identified in a 20 year old female with mild intellectual disability, superimposed expressive language disorder, and ADHD symptoms. X-inactivation analysis showed 84:16 ratio, consistent with moderate skewing.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677150	SCV000803310	uncertain significance	not provided	2018-04-03	criteria provided, single submitter	provider interpretation	This deletion was identified in an 8 year old female with developmental delays, severe superimposed expressive language disorder, uncertain overall intellectual abilities, ventricular septal defect, short stature, and hypertonia. Jaundice and sacral dimple were noted at birth. Notable facial features include: microcephaly, midface hypoplasia, triangular facies, fine hair, high forehead with broad and prominent brow, protruding low-set ears, epicanthus, deep-set eyes, sparse eyebrows, broad nasal root with low bridge, anteverted nares, small nasal tip, thin lips, small mouth, and small chin. She has proximally placed thumbs with small, abnormal nails. Renal ultrasound was normal. Additionally, a de novo, 23.7 Mb duplication on 9p was identified in this patient.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677151	SCV000803311	pathogenic	not provided	2018-04-03	criteria provided, single submitter	provider interpretation	This duplication was identified in an 8 year old female with developmental delays, severe superimposed expressive language disorder, uncertain overall intellectual abilities, ventricular septal defect, short stature, and hypertonia. Jaundice and sacral dimple were noted at birth. Notable facial features include: microcephaly, midface hypoplasia, triangular facies, fine hair, high forehead with broad and prominent brow, protruding low-set ears, epicanthus, deep-set eyes, sparse eyebrows, broad nasal root with low bridge, anteverted nares, small nasal tip, thin lips, small mouth, and small chin. She has proximally placed thumbs with small, abnormal nails. Renal ultrasound was normal. Additionally, a de novo, 212 kilobase deletion on 9p was identified in this patient.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677152	SCV000803312	uncertain significance	not provided	2018-04-05	criteria provided, single submitter	provider interpretation	This deletion was identified in a 14 year old male with intellectual disability, phonological disorder, ADHD, disruptive behavior, sleep disturbance, and constipation. Renal ultrasound revealed mild left-sided hydronephrosis, but kidneys were otherwise normal. The deletion was not found in his mother but the father was not available for testing. There is a paternal family history of behavior and developmental problems.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677153	SCV000803313	pathogenic	Chromosome 1p32-p31 deletion syndrome	2018-03-01	criteria provided, single submitter	provider interpretation	This deletion was identified in an 18 year old female with autism spectrum disorder, learning disorder, macrocephaly, and ADHD. Brain MRI at age 2 months showed thinned and high riding corpus callosum. The same deletion was identified in her younger twin sisters, who are more severely impaired, as well as her mother, who has some learning disability but who lives independently.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677154	SCV000803314	uncertain significance	Autism spectrum disorder due to AUTS2 deficiency	2018-04-03	criteria provided, single submitter	provider interpretation	This deletion was identified in a 12 year old female autism spectrum disorder, moderate intellectual disability, anxiety, history of seizures, short stature (less than 1st percentile), and low weight (1st percentile). The deletion was maternally inherited, and the mother has no history of neurodevelopmental disorders.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677155	SCV000803315	uncertain significance	not provided	2017-03-27	criteria provided, single submitter	provider interpretation	This duplication was identified in an 11 year old male with mild to moderate intellectual disability, hyperkinesis, atypical stereotypic movement disorder, disruptive behavior, borderline microcephaly (51.40 cm), short stature (2%ile), and dysmorphic features. The duplication was paternally inherited, and the patient's father is unaffected. Of note, this patient also carries a maternally-inherited VUS in EFNB1 and VUS of unknown inheritance in TLK2.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677156	SCV000803316	pathogenic	Generalized juvenile polyposis/juvenile polyposis coli	2017-05-01	criteria provided, single submitter	provider interpretation	This deletion was identified in an 8 year old male with autism spectrum disorder and intellectual disability. The patient has not yet had a colonoscopy or endoscopy but is scheduled to begin that surveillance at age 15. His cardiac evaluation was normal.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677157	SCV000803317	likely pathogenic	not provided	2017-05-01	criteria provided, single submitter	provider interpretation	This duplication was identified in an 8 year old male with autism spectrum disorder and intellectual disability. Given the size of the duplication, the variant has been classified as likely pathogenic.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677158	SCV000803318	uncertain significance	not provided	2018-04-16	criteria provided, single submitter	provider interpretation	This deletion was identified in a 12 year old female with a history of failure to thrive, infantile seizures, dysmorphic features, precocious puberty, and mild to moderate intellectual disability. Of note, Smith-Lemli-Opitz testing was negative.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677159	SCV000803319	uncertain significance	not provided	2018-03-22	criteria provided, single submitter	provider interpretation	This 123.5 kilobase deletion was detected in a patient with a history of choanal atresia, TE fistula, supraventricular tachycardia, renal reflux, craniosynostosis, congenital hydrocephalus, global developmental delay, bicuspid aortic valve, undesceneded testes, micropenis, and dysmorphic facial features. This deletion includes two OMIM genes CYP2E1 and SYCE1. This deletion was found to be maternally inherited. The patient's mother does not have a reported history of congenital anomalies or neurodevelopmental concerns. An additional variant identified in the patient was identified and felt to be consistent with CHARGE syndrome.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677160	SCV000803320	uncertain significance	not provided	2018-03-22	criteria provided, single submitter	provider interpretation	This approximately 747 kilobase duplication was identified in a male with autism spectrum disorder. This region includes 5 OMIM genes, of which VSP37A and FGF20 have been associated with clinical conditions. Both are associated with autosomal recessive conditions - spastic paraplegia 53 and renal hypoplasia/aplasia 2 respectively. Parental testing has not been completed to date.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677161	SCV000803321	uncertain significance	not provided	2018-04-04	criteria provided, single submitter	provider interpretation	This 2.6 Mb duplication was identified in a patient with a history of mild intellectual disability, superimposed severe expressive language disorder, congenital heart defect, seizure disorder, and rectal prolapse. The duplication includes approximately 25 known genes. Larger duplications have been reported in individuals with postnatal growth retardation, microcephaly, and characteristic facies (Grossman et al. 2009). This duplication was found to be paternally inherited. The patient's father has a history of speech delay and obesity.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677162	SCV000803322	uncertain significance	not provided	2018-03-22	criteria provided, single submitter	provider interpretation	This approximately 395 kilobase duplication was identified in a male with a history of microcephaly, congenital lymphedema of the feet, superimposed expressive language disorder, popliteal cysts and intellectual disability. The duplication includes 7 OMIM genes. Two of these genes are associated with known conditions - TUBB2A and TUBB2B. Heterozygous missense variants in TUBB2B are associated with microcephaly, brain abnormalities, developmental delays, intellectual disability, and seizures. Heterozygous missense variants in TUBB2A have been associated with hypotonia, brain abnormlities, seizures, and intellectual disability. The effect of a duplication of these genes is unclear. This duplication was found to be paternally inherited. The patient's father has a reported history of a learning disability and speech delay.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677163	SCV000803323	uncertain significance	not provided	2018-04-03	criteria provided, single submitter	provider interpretation	This approximately 3.3 Mb deletion was detected in an individual with a history of intellectual disability, dyspraxia, hypotonia, epicanthal folds, long facies with bitemporal narrowing, scoliosis, and increased joint laxity. A smaller, nested deletion was described in a patient with developmental delay, muscle hypotonia, dysmorphic features, and skeletal abnormalities (Shimojima et al. 2009). Several similar deletions have also been submitted to ClinVar (SCV000178752; SCV000175474; SCV000502982; SCV000502982). Parental testing has not been completed to date.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677164	SCV000803324	uncertain significance	not provided	2018-04-03	criteria provided, single submitter	provider interpretation	This 127.2 kilobase deletion was identified in a 10 year old with a history of autism spectrum disorder, mild impairments of visual-motor/problem-solving skills, and hyperkinesis. Parental testing has not been completed to date. A 1q21.1 duplication (including TAR region) was also identified in this patient.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677165	SCV000803325	uncertain significance	not provided	2017-12-01	criteria provided, single submitter	provider interpretation	This 582 kilobase duplication was identified in an individual with a history of developmental delay with borderline intellectual ability, developmental language impairment, umbilical hernia, and unilateral inguinal hernia. It includes 8 genes: CRLD2, CSF2RA, IL3RA, SLC25A6, ASMTL-AS1, ASMTL, P2RY8, AKAP17A, ASMT. The majority of these genes are not associated with known conditions. The CSF2RA gene is associated with hereditary pulmonary alveolar proteinosis, caused by loss of function of CSF2RA due to gene deletion or protein truncation. The ASMT gene has been implicated as potentially associated with autism spectrum disorders. Several association studies have published a possible increased risk for autism; however, additional studies failed to duplicate this association. Additionally, one publication (Cai et al. 2008) found an interstitial duplication of ASMT at a higher frequency in individuals with autism spectrum disorders compared to controls. This duplication included at least exons 2-8 of ASMT. The significance of entire gene duplications is unclear. Parental testing has not been completed to date.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677166	SCV000803326	likely pathogenic	not provided	2018-03-22	criteria provided, single submitter	provider interpretation	This 720.71 kilobase deletion was identified in a male with a history of autism spectrum disorder, developmental delay, and short stature. The deletion includes the 5' end of the NRXN1 gene and deletes exons 1-5 of the alpha isoform. Variants in the NRXN1 gene, including intragenic copy number variants, have been associated with a variable neurodevelopmental diagnoses including autism spectrum disorders, intellectual disability, epilepsy, and schizophrenia. The features are variable from individual to individual. 2p16.3 deletions and variants in the NRXN1 gene have also been reported in healthy controls and unaffected parents of individuals with neuropsychiatric disorders indicating reduced penetrance or variable expressivity (Schaaf et al. 2012; Bena et al. 2013).
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677167	SCV000803327	likely pathogenic	not provided	2018-03-22	criteria provided, single submitter	provider interpretation	This 714.9 kilobase deletion was identified in a male with a history of developmental language disorder, patent foramen ovale, microcephaly, apraxia of speech, and scoliosis. This deletion includes the distal portion of the common 22q11.21 region, but does not include the TBX1 gene and is proximal to BCR. Similar deletions have been reported in individuals with a number of features including growth restriction, developmental delay, intellectual disability, language delay, and dysmorphic features (Burnside 2015; Rauch et al. 2005). The patient's mother reportedly has a history of kyphosis, spinal tumor, and had a normal microarray.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677168	SCV000803328	uncertain significance	not provided	2018-04-03	criteria provided, single submitter	provider interpretation	This 1.93 Mb deletion was identified in a 9 year old female with microcephaly, mild intellectual disability, and ADHD. This deletion includes four genes, two of which are associated with known conditions. Single nucleotide variants in CHMP2B have been associated with familial frontotemporal lobar degeneration and amyotrophic lateral sclerosis 17. Frontotemporal dementia due to variants in this gene are thought to result from a build-up of the abnormal protein. The impact of a whole gene deletion is unclear, however. Homozygous or compound heterozygous variants in POU1F1 have been associated with autosomal recessive combined pituitary hormone deficiency. Maternal inheritance of the variant was ruled out, but paternal testing has not been completed. Subsequent whole exome sequencing identified two VUSs in a gene associated with an autosomal recessive condition.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677169	SCV000803329	uncertain significance	not provided	2018-03-28	criteria provided, single submitter	provider interpretation	This deletion was identified in a 10 year old male with mild hypotonia, autism spectrum disorder, learning disorder, OCD, ADHD, macrocephaly, borderline to mildly impaired verbal abilities with a large verbal/performance split, and was found to be paternally inherited. Proband's father has a history of depression and ADHD, along with a family history of autism. This deletion is within the RBFOX1 (also known as A2BP1) gene, which has not been clearly associated with human diseases. RBFOX1 has been implicated in a range of neurodevelopmental diseases including forms of epilepsy and autism spectrum disorders. It is not clear whether this deletion is related to the patient's neurodevelopmental history.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677170	SCV000803330	uncertain significance	not provided	2018-03-30	criteria provided, single submitter	provider interpretation	This duplication was identified in a 13 year old male with borderline intellectual functioning, superimposed expressive communication impairment/verbal apraxia, sleep disturbance, mood lability, irritability, and aggression. Parental testing for this duplication was not completed. Proband is a known carrier of a pathogenic 16p11.2 deletion, to which his symptoms are attributed. Within this duplication three OMIM genes are included; NF2, NEFH, and a portion of EWSR1. The clinical significance of a duplication of these genes is not currently known.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677171	SCV000803331	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2018-04-12	criteria provided, single submitter	provider interpretation	This deletion was identified in a 12 year old male with intellectual disability, autism spectrum disorder, anxiety, and obesity. Parental testing was not completed. This deletion includes three genes, including a portion of BRCA2. The patient's father has a strong family history of breast cancer in individuals under the age of 40 and so the deletion is likely paternally inherited. The father has a history of eye problems (ptosis, pain, diplopia), hypertension, and high cholesterol. Patient has a sister with autism who has not been tested for this deletion. The clinical significance of this deletion for the patient's current symptoms remains unclear at this time.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677172	SCV000803332	uncertain significance	not provided	2018-04-13	criteria provided, single submitter	provider interpretation	This duplication was identified in a 12 year old male with ADHD, oppositional defiant disorder, and a history of language disorder, and was found to be paternally inherited. The patient's father was born with bilateral polydactyly and a congenital heart anomaly. This duplication includes 4 genes, none of which are currently associated with a known clinical syndrome. DECIPHER reports one individual with a small duplication within this region in an individual with hypotonia, intellectual disability/developmental delay, microcephaly, proportionate short stature, and strabismus. The clinical significance of three copies of these genes remains unclear at this time.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677173	SCV000803333	pathogenic	Charcot-Marie-Tooth disease type 1B; Variegate porphyria; Migraine, familial hemiplegic, 2; Paragangliomas 3	2018-04-13	criteria provided, single submitter	provider interpretation	This deletion was identified in a 21 year old female with developmental delays and intellectual disability. Parental testing was not completed. This deletion contains approximately 50 genes including MPZ, PPOX, ATP1A2, and SDHC. She is at risk for developing Charcot-Marie-Tooth syndrome (type 1B, 2I, 2J, and dominant intermediate D), porphyria variegata, Hereditary Paraganglioma and Pheochromocytoma syndrome, and has an increased risk for migraines based on this deletion. Notably, she currently has no muscular symptoms consistent with CMT, nor any skin findings consistent with porphyria. Similar overlapping deletions have been seen in individuals with symptoms included but not limited to: intellectual disability, proportionate short statue, dysmorphic features, bilateral cleft lip/palate, hemiatrophy, hypodysplasia of corpus callosum, IUGR, and complex heart defects. This individual also has 16p11.2 deletion syndrome, identified through chromosomal microarray, which is also likely contributing to her developmental phenotype.
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000754985	SCV000803395	uncertain significance	Intestinal malrotation	2018-06-11	criteria provided, single submitter	research
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000754986	SCV000803396	likely pathogenic	Intestinal malrotation	2018-06-11	criteria provided, single submitter	research
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000754987	SCV000803397	uncertain significance	Intestinal malrotation	2018-06-11	criteria provided, single submitter	research
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000754988	SCV000803398	pathogenic	Intestinal malrotation	2018-06-11	criteria provided, single submitter	research
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000754989	SCV000803399	pathogenic	Intestinal malrotation	2018-06-11	criteria provided, single submitter	research
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677908	SCV000804063	likely pathogenic	Cystinuria	2016-06-16	criteria provided, single submitter	provider interpretation	This deletion was identified in a 6 year old female with developmental delays, microcephaly, craniosynostosis, hypertrophic cardiomyopathy, and history of acute lymphoid leukemia in remission. This deletion was inherited from a mother with a history of a kidney stone and the maternal grandfather is reported to have multiple kidney stones. Follow up testing for the proband showed elevated urine amino acids. This result indicates carrier status for cystinuria, at minimum. Additionally, 3 variants of uncertain significance were identified by exome sequencing.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677909	SCV000804064	uncertain significance	not provided	2018-03-19	criteria provided, single submitter	provider interpretation	This duplication was identified in a 5 year old male with global developmental delay. Brain MRI at age 26 months showed a slightly delayed myelination pattern. Parental testing was not completed. There is a family history of learning and psychiatric illness on both the maternal and paternal side, and a paternal family history of seizures. No facial dysmorphisms were noted.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677910	SCV000804065	pathogenic	not provided	2018-04-03	criteria provided, single submitter	provider interpretation	This deletion was identified in a 5 year old male with global developmental delays, velopharyngeal insufficiency, VSD, PFO, recurrent otitis media, mild astigmatism, bilateral single transverse palmar creases, narrow left palpebral fissure, full lips, bowed upper lip, and 5th finger clinodactyly. Brain MRI showed mega cisterna magna but was otherwise unremarkable. Parental testing was not completed.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677911	SCV000804066	uncertain significance	not provided	2018-04-03	criteria provided, single submitter	provider interpretation	This duplication was identified in a 5 year old male with global developmental delays, velopharyngeal insufficiency, VSD, PFO, recurrent otitis media, mild astigmatism, bilateral single transverse palmar creases, narrow left palpebral fissure, full lips, bowed upper lip, and 5th finger clinodactyly. Brain MRI showed mega cisterna magna but was otherwise unremarkable. Parental testing was not completed. Additionally, a 2.478 Mb pathogenic chromosomal deletion was identified in this patient.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677912	SCV000804067	uncertain significance	not provided	2018-04-03	criteria provided, single submitter	provider interpretation	This duplication was identified in a 6 year old female with slightly upslanted palpebral fissures and autism spectrum disorder. She was born at term with significant issues in the neonatal period including meconium aspiration with respiratory distress, hypotension, metabolic acidosis, HIE, persistent fetal circulation, adrenal hypofunction, thrombocytopenia, and anemia. Parental testing was not available.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677913	SCV000804068	uncertain significance	not provided	2018-02-05	criteria provided, single submitter	provider interpretation	This deletion was identified in a 5 year old female with autism spectrum disorder, global developmental delays, hyperkinesis, ADHD, feeding problems, sleep problems, and wide spaced teeth. The deletion was inherited from a father with ADHD and bipolar disorder. Follow up ophthalmological exam was normal and the father has normal vision. This history supports the putative PAX6 downstream regulatory region proposed by Balay et al, 2015 (PMID:26419218), which is not included in this patient's deletion region. It is not clear whether this deletion is related to the patient neurodevelopmental history.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677914	SCV000804069	uncertain significance	not provided	2018-04-03	criteria provided, single submitter	provider interpretation	This deletion was identified in a 20 year old male with autism spectrum disorder, sleep disturbance, mood disorder, anxiety, macrocephaly, a vocal tic, and obesity. He has astigmatism, eczema, and a history of frequent epistaxis. There is no paternal history of neurodevelopmental disorders.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677915	SCV000804070	likely benign	not provided	2018-04-05	criteria provided, single submitter	provider interpretation	This deletion was identified in a 7 year old male with a history of global developmental delay (intellectual ability are uncertain) and superimposed expressive language delay. He has echolalia and will point in a protoimperative and protodeclarative manner. He is making progress with expressing emotions and will follow a familiar two-step command. He was found to have a pathogenic 8.2 Mb duplication of 18p11.32p11.22 by microarray.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677916	SCV000804071	pathogenic	not provided	2018-04-05	criteria provided, single submitter	provider interpretation	This duplication was identified in a 7 year old male with a history of global developmental delay (intellectual ability are uncertain) and superimposed expressive language delay. He has echolalia and will point in a protoimperative and protodeclarative manner. He is making progress with expressing emotions and will follow a familiar two-step command. The duplication was also found in the patient's mother, who has a history of ADHD and learning disability.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677917	SCV000804072	uncertain significance	not provided	2018-04-05	criteria provided, single submitter	provider interpretation	This duplication was identified in a 9 year old male with mild intellectual disability, expressive language delay, inattentiveness, and hyperkinesis. The duplication was inherited from a mother with no significant neurodevelopmental problems.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677918	SCV000804073	pathogenic	not provided	2018-04-05	criteria provided, single submitter	provider interpretation	This deletion was identified in a 5 year old male with global developmental delays, mild neuromotor abnormalities, stereotypy, macrocephaly, and large stature. He is monitored for seizures due to spells. He has had normal cardiac echo and ECG, normal cranial ultrasound, normal renal ultrasound (except for a urachal cyst). The deletion was inherited from a father with a history of speech delay, learning disability, bipolar disorder, depression, anxiety, substance abuse, heart murmur, and congenital pancreatic divisum.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677919	SCV000804074	likely benign	not provided	2018-02-26	criteria provided, single submitter	provider interpretation	This duplication was identified in a 10 year old male with autism spectrum disorder, large stature, anxiety, compulsive behavior, and uncertain intellectual abilities. The duplication was inherited from the patient's mother, who does not report learning or developmental problems. There is a maternal family history of psychiatric illness. Additionally, a de novo copy number gain at 19p13.2 was identified by CMA, and 2 variants of uncertain significance were identified by exome sequencing.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677920	SCV000804075	uncertain significance	not provided	2018-02-26	criteria provided, single submitter	provider interpretation	This duplication was identified in a 10 year old male with autism spectrum disorder, large stature, anxiety, compulsive behavior, and uncertain intellectual abilities and was found to be de novo. Additionally, a maternally-inherited copy number gain at 6p22.3 was identified by CMA, and 2 variants of uncertain significance were identified by exome sequencing.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677921	SCV000804076	likely pathogenic	not provided	2018-02-05	criteria provided, single submitter	provider interpretation	This duplication was identified in a 9 year old male with agenesis of the corpus callosum, macrocephaly secondary to enlarged third ventricle, ADHD, and a family history of psychiatric illness. His biological mother has agenesis of the corpus callosum, Tourette's syndrome, and depression. A maternal uncle has schizophrenia, agenesis of the corpus callosum, seizure disorder, and bipolar disorder. The maternal grandfather had schizophrenia and agenesis of the corpus callosum, and a maternal great uncle also had agenesis of the corpus callosum. Parental or other family member testing was not possible. This duplication includes the SHH gene and additional duplications in the literature suggest it is causative for this patient's clinical features (Heide, 2017; Wong, 2015).
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677922	SCV000804077	likely pathogenic	Severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome	2018-02-05	criteria provided, single submitter	provider interpretation	This deletion was identified in a 4 year old female with global developmental delays, macrocephaly, telecanthus, and a wide based gait. It was found to be de novo and likely impacts expression of the GATAD2B gene due to loss of regulatory region. Clinical correlation with previously reported patients with GATAD2B-related disorder was thought to be very good. In addition, this patient has a paternally-inherited, likely benign duplication at 4q22.3.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677923	SCV000804078	likely benign	not provided	2018-02-05	criteria provided, single submitter	provider interpretation	This duplication was identified in a 4 year old female with global developmental delays, macrocephaly, telecanthus, and a wide based gait. It was inherited from a clinically unaffected father. In addition, this patient carries a de novo, likely pathogenic deletion at 1q21.3.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677924	SCV000804079	uncertain significance	not provided	2018-02-26	criteria provided, single submitter	provider interpretation	This duplication was identified in a 17 year old male with learning disorder and high functioning autism spectrum disorder. He has a recent diagnosis of sinus tachycardia. This duplication was inherited from the patient's mother, who has a history of anxiety disorder and obsessive-compulsive disorder. Her identical twin sister has a history of depression and severe obsessive-compulsive disorder. This patient's sister, who has mild autism and a phonological disorder, also carries this duplication.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677925	SCV000804080	uncertain significance	not provided	2018-02-05	criteria provided, single submitter	provider interpretation	This duplication was identified in a 4 year old male with mild global developmental delays, receptive/expressive language disorder, hypotonia, microcephaly, and short stature. Brain MRI revealed pachygyria. Ophthalmology and endocrinology evaluations were normal. This patient's mother, who carries this variant, has learning disability. She has not had subsequent brain imaging. In addition, this patient and his mother were found to carry a novel missense variant in the TUBB2B gene.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677926	SCV000804081	pathogenic	not provided	2018-04-05	criteria provided, single submitter	provider interpretation	This duplication was identified in a 4 year old female with global developmental delays, hearing impairment, sleep problems, short stature, esotropia, chronic constipation, anemia, and small PFO. Renal ultrasound was normal. Notable facial features include a long, narrow face, upslanting palpebral fissures, infraorbital creases, bulbous nasal tip, anteverted nares, and mild retrognathia. This patient also has a pathogenic 39 Mb terminal deletion of Xp22.3p11.2. These copy number variants are a result of a de novo rearrangement: 46,X,der(X)t(X;15)(p11.4;q11.2).
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677928	SCV000804083	likely benign	not provided	2018-02-26	criteria provided, single submitter	provider interpretation	This duplication was identified in a 6 year old male with a language disorder, delayed adaptive skills, hypotonia, and short stature. It was inherited from his clinically unaffected mother, who also has no vision abnormalities. Copy number gains of the GUCA1A and GUCA1B genes have been observed in the ExAC database.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677929	SCV000804084	uncertain significance	not provided	2017-06-12	criteria provided, single submitter	provider interpretation	This duplication was identified in a 3 year old female with develomental delays. She is non-dysmorphic and has a strong maternal family history of psychiatric disorders, seizures, and intellectual disability. Paternal history is unknown. Parental samples were not available for testing. Additionally, a variant of uncertain significance was identified by whole exome sequencing.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677930	SCV000804085	uncertain significance	not provided	2017-08-03	criteria provided, single submitter	provider interpretation	This deletion was identified in a 3 year old male with global developmental delay, expressive language disorder, mild hypotonia, short stature, dolichocephaly, laterally arched eyebrows, epicanthal folds, bulbous nasal tip, bowed upper lip, small toes, sleep disorder, and a history of prematurity. It was inherited from an unaffected mother. It is also a fairly gene-poor region. Additionally, whole exome sequencing identified a de novo, likely pathogenic sequence variant which most likely explains this patient's clinical history.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677931	SCV000804086	pathogenic	Becker muscular dystrophy	2017-05-16	criteria provided, single submitter	provider interpretation	This deletion was identified in a 10 year old male with mild intellectual disability, ADHD, oppositional-defiant disorder, and a history of gastroschisis. Muscle tone and strength appeared normal on exam and there were no gait abnormalities. CK levels, taken after identification of DMD deletion, were significantly elevated (2287).
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677932	SCV000804087	pathogenic	not provided	2017-10-31	criteria provided, single submitter	provider interpretation	This deletion was identified in a 4 year old female with autism spectrum disorder, global developmental delay, and mild hypotonia. She walked at age 2 but currently there are no motor concerns. She has significant language delay with no spoken words, does not point to request, and appears to understand only a few words (receptive age equivalent 10 months). She is slightly short (5th percentile). She has a long philtrum but is otherwise non-dysmorphic.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677933	SCV000804088	uncertain significance	not provided	2018-03-29	criteria provided, single submitter	provider interpretation	This deletion was identified in a 6 year old male with autism spectrum disorder, disruptive behavior, hyperactivity, persistent insomnia, coordination disorder, and cyclic vomiting syndrome. Only a maternal sample was available for testing, and the patient's mother does not carry the deletion. Of note, this patient also carries a variant of uncertain significance in the ADCY5 gene.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677934	SCV000804089	pathogenic	Chromosome 2p16.3 deletion syndrome	2017-07-29	criteria provided, single submitter	provider interpretation	This deletion was identified in a 5 year old male with mild intellectual disability, ADHD, mild phonological disorder, and disruptive behavior disorder. Parental testing was not completed. There is an extensive family history of substance abuse, psychiatric diagnoses, and learning disabilities. Two additional copy number variants were also identified in this patient, one likely pathogenic and one of uncertain significance.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677935	SCV000804090	likely pathogenic	Spinocerebellar ataxia type 27	2017-07-29	criteria provided, single submitter	provider interpretation	This deletion was identified in a 5 year old male with mild intellectual disability, ADHD, mild phonological disorder, and disruptive behavior disorder. Parental testing was not completed. There is no family history of movement disorders. The patient does not currently show any signs of tremor, dyskinesia, or ataxia. He is described by his family as more uncoordinated than his peers. There are reports of individuals with FGF14-related cerebellar ataxia not presenting with motor abnormalities until later in childhood, so the patient will continue to be monitored. Two additional copy number variants were also identified in this patient, one that is pathogenic and one of uncertain significance.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677936	SCV000804091	uncertain significance	not provided	2017-07-29	criteria provided, single submitter	provider interpretation	This duplication was identified in a 5 year old male with mild intellectual disability, ADHD, mild phonological disorder, and disruptive behavior disorder. Parental testing was not completed. The region is not known to vary in copy number in the normal population, but none of the genes in the region are currently associated with known clinical disorders. Two additional copy number variants were also identified in this patient, one that is pathogenic and one that is likely pathogenic.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677937	SCV000804092	uncertain significance	not provided	2014-11-12	criteria provided, single submitter	provider interpretation	This deletion was identified in a 7 year old male with global developmental delays, phonological disorder, ADHD, and disruptive behavior. The deletion was inherited from his mother, who has a history of learning disabilities and ADHD. The deletion is also present in the patient's brother, who has a history of abnormal number of umbilical cord vessel, cardiac defect, and bilateral clubfoot deformity.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677938	SCV000804093	pathogenic	Autosomal recessive nonsyndromic hearing loss 16	2018-03-29	criteria provided, single submitter	provider interpretation	This deletion was identified in a 3 year old female with bilateral sensorineural hearing loss, mixed receptive-expressive language disorder, mild visual-motor delay, mild hypotonia, and gross motor delay. While parental studies have not been done, both of the patient's sisters are homozygous for the same 15q15.3 deletion and both have hearing impairments, suggesting that the parents are each a carrier of the deletion.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677939	SCV000804094	pathogenic	Becker muscular dystrophy; Duchenne muscular dystrophy; Dilated cardiomyopathy 3B	2017-02-06	criteria provided, single submitter	provider interpretation	This deletion was identified in an 8 year old female with autism spectrum disorder and intellectual disability. The deletion was maternally inherited, and the mother has a history of language delays in childhood, learning impairment, depression, anxiety, and bipolar disorder. She reported a family history of Duchenne muscular dystrophy. One of the patient's maternal uncles died at age 21, and another maternal uncle died at age 12 following anesthesia complications during surgery; they were both reported to have DMD. Neither the patient nor her mother have been evaluated by cardiology to assess for cardiomyopathy. Additionally, neither the patient nor her mother have a history of muscle weakness or gait abnormalities.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677940	SCV000804095	likely pathogenic	Nemaline myopathy 6	2018-04-12	criteria provided, single submitter	provider interpretation	This deletion was identified in a 12 year old male with autism spectrum disorder, history of right talipes equinovarus, and leg length discrepancy. Parental studies (targeted microarray and FISH analysis) revealed that this deletion arose de novo.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677941	SCV000804096	uncertain significance	not provided	2018-04-13	criteria provided, single submitter	provider interpretation	This duplication was identified in a 12 year old male with intellectual disability and history of multiple non-traumatic fractures. While this duplication was de novo, the patient's father has a history of multiple fractures. Of note, this patient has had negative sequencing and deletion/duplication analaysis of the COL1A1 and COL1A2 genes.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677942	SCV000804097	pathogenic	not provided	2018-04-15	criteria provided, single submitter	provider interpretation	This duplication was identified in a 5 year old female with global developmental delays, short stature, basiocciput hyperplasia and associated basilar invagination, and an arachnoid cyst. Parental studies were performed, and the duplication was found to be de novo.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677943	SCV000804098	pathogenic	Axenfeld-Rieger syndrome type 3	2018-04-16	criteria provided, single submitter	provider interpretation	This deletion was identified in a 9 year old female with intellectual disability, microcephaly, craniosynostosis, left hemifacial microsomia, feeding disorder, congenital heart defects, congenital hypothyroidism, renal hypodysplasia/stage 3 chronic kidney disease, ptosis, alternating esotropia, recurrent otitis media, small teeth, and history of prematurity (born at 34 weeks). The deletion was inherited from the patient's father who carries a balanced chromosome translocation (46,XX,der(21),t(6;21)(p21.3q22.3)pat). Because of the patient's intolerance to opthalmological exams, it is not known whether or not she shows signs of glaucoma.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677944	SCV000804099	pathogenic	not provided	2018-04-16	criteria provided, single submitter	provider interpretation	This duplication was identified in a 9 year old female with intellectual disability, microcephaly, craniosynostosis, left hemifacial microsomia, feeding disorder, congenital heart defects, congenital hypothyroidism, renal hypodysplasia/stage 3 chronic kidney disease, ptosis, alternating esotropia, recurrent otitis media, small teeth, and history of prematurity (born at 34 weeks). The duplication was inherited from the patient's father who carries a balanced chromosome translocation (46,XX,der(21),t(6;21)(p21.3q22.3)pat).
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677945	SCV000804100	uncertain significance	not provided	2017-10-09	criteria provided, single submitter	provider interpretation	This duplication was identified in a 4 year old male with global developmental delays. The duplication was paternally inherited, and the patient's father has a history of learning disabilities and bipolar disorder. The region is not known to vary in copy number in the normal population. The two genes in this region that are associated with human disease (SUMF1, ITPR1) are not known to cause disease when duplicated. Of note, this patient also carries the recurrent 22q11.2 duplication.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677946	SCV000804101	uncertain significance	not provided	2018-04-15	criteria provided, single submitter	provider interpretation	This duplication was identified in an 18 year old male with mild intellectual disability, ADHD, disruptive behavior, and microcephaly (5th percentile). The patient's mother does not carry the duplication, and a paternal sample is unavailable.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677947	SCV000804102	uncertain significance	not provided	2017-01-10	criteria provided, single submitter	provider interpretation	This deletion was identified in a 6 year old male with intellectual disability and motor stereotypies. The deletion was found to be maternailly-inherited; the patient's mother is unaffected. The deletion encompasses the non-coding exon 1 of RBFOX1. Haploinsuffiency of RBFOX1 has been implicated in several neurodevelopmental phenotypes, and some deletions have been inherited from a phenotypically normal parent. Of note, this patient also carries a paternally-inherited VUS in the SHANK2 gene.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677948	SCV000804103	uncertain significance	Dilated cardiomyopathy 1W; Hypertrophic cardiomyopathy 15	2015-10-30	criteria provided, single submitter	provider interpretation	This duplication was identified in a 4 year old female with autism spectrum disorder, global developmental delays, and a feeding disorder. Parental testing has not been performed. Family history is significant for a cerebrovascular accident in the patient's mother at age 36, but there is no known history of cardiomyopathy. Of note, this patient's whole exome sequencing has thus far been negative.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677949	SCV000804104	uncertain significance	Midface hypoplasia, hearing impairment, elliptocytosis, and nephrocalcinosis	2017-03-23	criteria provided, single submitter	provider interpretation	This duplication was identified in a 7 year old male with autism spectrum disorder. The duplication was maternally inherited, and his mother does not have a history of hearing impairment or learning disabilities. She does have a history of kidney stones; loss of function variants in AMMECR1, which is within this duplicated region, are associated with nephrocalcinosis. The patient does not have a history of any kidney concerns. Of note, the patient's whole exome sequencing has thus far been normal.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677950	SCV000804105	uncertain significance	not provided	2017-06-13	criteria provided, single submitter	provider interpretation	This duplication was identified in a 4 year old male with autism spectrum disorder and global developmental delays. The duplication was maternally inherited, and this individual's mother does not have a history of neurodevelopmental disorders.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677951	SCV000804106	uncertain significance	Autism spectrum disorder due to AUTS2 deficiency	2017-03-30	criteria provided, single submitter	provider interpretation	This duplication was identified in a 4 year old male with autism spectrum disorder, global developmental delays, and agenesis of the corpus callosum. The duplication was maternally-inherited, and the patient's mother has a history of depression and anxiety. The patient also carries a maternally inherited duplication of uncertain significance at 18q21.2. Of note, this patient's whole exome sequencing has thus far been normal.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677952	SCV000804107	uncertain significance	Mirror movements 1	2017-03-30	criteria provided, single submitter	provider interpretation	This duplication was identified in a 4 year old male with autism spectrum disorder, global developmental delays, and agenesis of the corpus callosum. The duplcation was inherited from his mother, who has a history of anxiety and depression. The patient also carries a duplication of uncertain significance at 7q11.22. Of note, his whole exome sequencing has thus far been negative.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677953	SCV000804108	uncertain significance	not provided	2017-03-26	criteria provided, single submitter	provider interpretation	This duplication was identified in a 7 year old male with autism spectrum disorder, history of developmental delays with uncertain intellectual abilities, and self-injurious behaviors. The duplication is maternally-inherited; the patient's mother has a history of anxiety and depression. Of note, the patient was found to carry a variant of uncertain significance in KIF4A through whole exome sequencing.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677954	SCV000804109	uncertain significance	not provided	2014-01-24	criteria provided, single submitter	provider interpretation	This deletion was identified in a 15 year old male with autism spectrum disorder, intellecutal disability, disruptive behavior, sleep disturbances, and staring episodes. The deletion was found to be maternally inherited; his mother has a history of depression and phenomic disorder.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677955	SCV000804110	uncertain significance	not provided	2017-05-01	criteria provided, single submitter	provider interpretation	This duplication was identified in a 16 year old female with autism spectrum disorder and intellectual disbaility. Parental studies were never performed, so inheritance is unknown.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677956	SCV000804111	uncertain significance	not provided	2016-12-08	criteria provided, single submitter	provider interpretation	This duplication was identified in a 3 year old male with autism spectrum disorder and global developmental delays. The duplication was paternally inherited, and the patient's father has a history of learning disabilities, childhood speech delay, childhood seizures, and anxiety.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677957	SCV000804112	uncertain significance	not provided	2017-06-08	criteria provided, single submitter	provider interpretation	This deletion was identified in a 16 year old male with intellectual disability and growth failure. Of note, this patient also carries a de novo likely pathogenic variant in the ZNF711 gene, which is felt to explain his intellectual disability. The patient's mother is unaffected.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677958	SCV000804113	pathogenic	Hyperparathyroidism 1; Parathyroid carcinoma; Hyperparathyroidism 2 with jaw tumors	2017-04-25	criteria provided, single submitter	provider interpretation	This deletion was identified in a 13 year old female with borderline intellectual disability, motor coordination disorder, ADHD, skull anomalies, history of neonatal seizure, and amblyopia. The patient's biological parents are unavailable for parental studies. There is no known family history of parathyroid cancer or thyroid disease. Of note, the patient also carries a pathogenic deletion at 16p11.2.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677959	SCV000804114	uncertain significance	not provided	2017-05-01	criteria provided, single submitter	provider interpretation	This duplication was identified in a 3 year old female with autism spectrum disorder and global developmental delays. The duplication is maternally-inherited, and the mother has no history of neurodevelopmental disorders.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677960	SCV000804115	uncertain significance	not provided	2017-05-17	criteria provided, single submitter	provider interpretation	This duplication was identified in a 4 year old female with global developmental delays and autism spectrum disorder. The duplication was found to be paternally inherited. The patient's father required learning supports in school.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677961	SCV000804116	uncertain significance	not provided	2017-05-19	criteria provided, single submitter	provider interpretation	This deletion was identified in an 11 year old male with left hemiplegia, mild intellectual disability, seizure disorder, and hypothyroidism. Parental samples are unavailable, so inheritance is unknown.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677962	SCV000804117	uncertain significance	Hypogonadotropic hypogonadism 1 with or without anosmia	2017-08-10	criteria provided, single submitter	provider interpretation	This duplication was identified in a 4 year old female with global developmental delays. Parental samples are unavailable, so inheritance is unknown.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677963	SCV000804118	uncertain significance	not provided	2018-01-31	criteria provided, single submitter	provider interpretation	This duplication was identified in a 4 year old male with autism spectrum disorder and speech delay. The duplication was found to be maternally inherited, and the patient's mother received learning supports in school.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677964	SCV000804119	pathogenic	Exudative vitreoretinopathy 1	2017-10-18	criteria provided, single submitter	provider interpretation	This deletion was identified in an 11 year old male with autism spectrum disorder and intellectual disability. The patient does not tolerate thorough opthalmological evaluations, but he is not reported to show any signs of retinopathy at his current age.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677965	SCV000804120	uncertain significance	Congenital plasminogen activator inhibitor type 1 deficiency	2017-10-18	criteria provided, single submitter	provider interpretation	This duplication was identified in an 11 year old male with autism spectrum disorder and intellectual disability. The duplication was maternally-inherited, and neither the patient nor his mother are reported to have abnormal bleeding after trauma or surgery.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677966	SCV000804121	uncertain significance	not provided	2018-04-11	criteria provided, single submitter	provider interpretation	This duplication was identified in a 12 year old male with autism spectrum disorder, ADHD, history of global developmental delay (resolved, IQ currently in average range), and history of bilateral clubfoot deformity. The duplication was paternally inherited, and the patient's father has learning difficulties and a history of anxiety and depression.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677967	SCV000804122	uncertain significance	not provided	2018-04-13	criteria provided, single submitter	provider interpretation	This duplication was identified in a 6 year old male with autism spectrum disorder, global developmental delay, hypotonia, a heart murmur, feeding problems, GERD, and a history of a unilaterial inguinal hernia, and was found to be maternally inherited. The patient's mother does not have a history of any neurodevelopmental disorders. Notably, neither this patient nor his mother have any hand, foot, or bone defects.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677968	SCV000804123	uncertain significance	not provided	2018-04-13	criteria provided, single submitter	provider interpretation	This duplication was identified in a 6 year old male with autism spectrum disorder, global developmental delay, hypotonia, a heart murmur, feeding problems, GERD, and a history of a unilaterial inguinal hernia. The duplication was found to be maternally inherited. The patient's mother does not have a history of any neurodevelopmental disorders.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677969	SCV000804124	uncertain significance	Macrocephaly, macrosomia, facial dysmorphism syndrome	2018-02-23	criteria provided, single submitter	provider interpretation	This duplication was identified in a 4 year old male with autism spectrum disorder, global developmental delay, and history of prematurity (born at 28 weeks). The duplication was maternally inherited, and the mother has a history of learning disability and depression.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677970	SCV000804125	uncertain significance	not provided	2017-08-21	criteria provided, single submitter	provider interpretation	This 924 kilobase duplication includes portions of the NKAIN2 and TRDN genes. TRDN is associated with autosomal recessive catecholaminergic polymorphic ventricular tachycardia-5 with or without muscle weakness. NKAIN2 is not currently associated with any known disorders. Disruption of NKAIN2 due to de novo rearrangements have been reported in two patients previously (Yue et al. 2006; Bocciardi et al. 2005). One individual with disruption at exon 4 had a clinical history of a congenital heart defect, macrocephaly, undescended testes, recurrent infections, and developmental delays (Yue et al. 2006). The second individual's translocation disrupted the gene in intron 4 had a history of neurologic abnormalities including including epileptic encephalopathy with spastic tetraparesis and severe psychomotor retardation associated with cerebral atrophy with involvement of the periventricular white matter (Bocciardi et al. 2005). Similar, overlapping duplications have been reported in several individuals in DECIPHER including in an individual with cognitive impairment (Case: 300577) and an individual with short stature (Case:331671). Overlapping variants have also been submitted to dbVar/ClinVar previously (nssv582678; nsv2777188; nsv534388) and reported in developmental delay cohorts as well as in controls (nsv1022195; nsv1018599). A similar duplication has been reported in the literature in an individual with facial dysmorphism, severe developmental delay, complex neurological impairment and spasticity (Sheth et al. 2015). Both unaffected, consanguinous parents carried that duplication, however. Given that similar duplications have been reported in individuals with neurodevelopmental concerns as well as in control populations and unaffected parents, the clinical significance of this variant is unclear. This patient also had a maternally inherited, pathogenic 1q21.1q21.2 duplication identified on chromosomal microarray that provides an explanation for his autism spectrum disoder, speech delay, and other phenotypic features.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677971	SCV000804126	uncertain significance	not provided	2017-10-31	criteria provided, single submitter	provider interpretation	This 259 kilobase duplication includes a portion of the PARK2 gene. The PARK2 gene is associated with autosomal recessive juvenile parkison disease type 2. Copy number variants (deletions and duplications) including PARK2 have been reported at a higher prevalence in individuals with ADHD compared to controls, suggesting deletions and duplications of PARK2 may be associated with increased susceptibility of ADHD (Jarick et al. 2014). Deletions and duplications including PARK2 have been suggested as a possible genetic suscpetibility of autism spectrum disorder (Glessner et al. 2009; Yin et al. 2016). A duplication also has been identified in an individual with cognitive impairments who is underweight and has short stature (Scheuerle & Wilson 2011). PARK2 partial gene duplications have been reported in DECIPHER in individuals with intellectual disability and behavioral abnormalities (279450; 279451). The copy number variants reported previously contain multiple exons, whereas, this patient's duplication only includes exon 2 of the gene. PARK2 copy number variants have also been identified in control populations (nsv605163; nsv605167; nsv1034495; nsv1021711; nsv1019976). Follow-up quantitative PCR confirmed overexpression of PARK2 in both the patient and his father suggesting this duplication was paternally inherited. The patient's father has a reported history of dyslexia and learning disability in early schooling. Based on the relatively low number of patients reported in the literature and the presence of duplications and deletions in healthy controls/unaffected parents, further evidence is needed to definitively classify this variant. Whole exome sequencing was also completed for this patient and a paternally inherited variant of uncertain significance was identified.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677973	SCV000804128	uncertain significance	not provided	2017-10-30	criteria provided, single submitter	provider interpretation	The 211 kilobase duplication on chromosome 22 contains 4 genes (TXN2, FOXRED2, EIF3D, and a portion of CACNG2), none of which are known to be associated with a clinical disorder when duplicated. The TXN2 gene is associated with autosomal recessive oxidative phosphylation deficiency- 29 and CACNG2 has been reported to cause autosomal dominant intellectual disability due to loss of function variants. A smaller overlapping duplication was identified in a developmental delay cohort (nsv1064827). An overlapping duplication has also been reported in a control (nsv1060004). Parental testing for our patient showed that this variant was paternally inherited. The patient's father does not have a history of autism spectrum disorders or developmental differences making this variant less likely to be anexplanation for the patient's neurodevelopmental history. The patient also underwent whole exome sequencing that identified a de novo variant in a gene of uncertain significance.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677974	SCV000804129	uncertain significance	not provided	2018-02-02	criteria provided, single submitter	provider interpretation	This 507 kilobase duplication was detected in an individual with developmental delay, autism spectrum disorder, dermititis, and sleep difficulties. This duplication includes a portion of the TWIST2 and HDAC4 genes. TWIST2 is associated with the autosomal recessive disorder focal facial dermal dysplasis 3, Setleis type. Haploinsufficiency of HDAC4 is associated with brachydactyly-mental retardation syndrome. Duplications of these genes have not been associated with any particular conditions, however. The genetic testing laboratory indicated that they have seen duplications in the area, and several other duplications have been reported in DECIPHER, including a smaller overlapping variant in an individual with an abnormal face shape and intellectual disability (Case: 282651). This area is not known to vary in the general population. Parental testing has not been completed to date to determine if this variant is de novo or inherited.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677975	SCV000804130	likely pathogenic	not provided	2017-11-16	criteria provided, single submitter	provider interpretation	This approximately 9.1 Mb deletion was detected in a 10 year old male with a history of expressive language disorder, autism spectrum disorder, sleep difficulties, and ADHD. This deletion includes 25 genes, 4 of which have been associated with clinical disorders. Two genes, NEK1 and MSMO1, are associated with autosomal recessive conditions indicating the patient is a carrier for these conditions. Heterozygous missense variants in the TLL1 gene have been associated with atrial septal defects (Stanczak et al. 2009). A single missense variant in PALLD has been reported to increase susceptibility to pancreatic cancer. PALLD has conflicting literature regarding its link to pancreatic cancer risk, however. Some publications indicate a risk while other literature refutes this. Functionally, this variant has been shown to result in overexpression of the gene, and overexpression of the gene is not expected with a gene deletion (Pogue-Geile et al. 2006). Overlapping deletions have been reported in the literature in an individual with Robin sequence, mild developmental delays and ulnar anomalies and another individual with congenital heart defect, growth delay, and minor skeletal anomalies (Keeling et al. 2001; Xu et al. 2012). Overlapping deletions have been identified in several individuals in DECIPHER including an individual with a broad forehead, downslanted palpebral fissures, high anterior hairline, and intellectual disability (Case 257358). An overlapping variant was also submitted to ClinVar/dbVar in an individual with abnormal facial shape and learning disability (nsv532029). A follow-up echocardiogram for the patient was normal. Parental follow-up testing identified that this deletion is secondary to a maternal balanced rearrangement. Maternal family history includes a relative with multiple miscarriages, a pregnancy with congenital anomaly of the brain/skull, and a child with a congenital heart defect suggesting others in the family may also carry the balanced rearrangement.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677976	SCV000804131	uncertain significance	not provided	2018-03-16	criteria provided, single submitter	provider interpretation	This 305 kilobase duplication was identified in an individual with autism spectrum disorder, delayed milestones, hyperopia, and asthma. This duplication includes portions of the SHOX and PPP2R3B genes. Nonsense variants and deletions of SHOX have been reported in individuals with idiopathic short stature and Leri-Weill dyschondrosteosis (Huber et al. 2001; Niesler et al. 2002; Rappold et al. 2002). Partial or complete duplications of SHOX and/or its enhancer regions have also been reported in patients with these conditions (Thomas et al. 2009; Benito-Sanz et al. 2011). Duplications of SHOX have also been reported in individuals with tall stature. Tropeano et al. 2016 identified an enrichment of SHOX microduplications in individuals with neurodevelopmental disorders including autism sprectrum disorders compared to controls. The patient's father also was found to carry this duplication although testing could not determine if the variant is on his father's X or Y chromosome since its location on the Y chromosome in the patient could be the result of recombination between the X and Y chromosomes in his father. The patient's father is also of typical height but does have a reported history of speech delay and learning disability. The patient was found to also carry a maternally inherited, distal 16p11.2 deletion.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677977	SCV000804132	uncertain significance	not provided	2018-03-19	criteria provided, single submitter	provider interpretation	This 393 kilobase duplication was identified in an individual with autism spectrum disorder, intellectual disability, ADHD, constipation, hypotonia, and expressive language disorder. This duplication is within cytogenetic band 16p13.3. The duplication includes 15 entire genes and the portion of two additional genes. Four genes are associated with clinical conditions - TSC2, PKD1, ABCA3, and TBC1D24. A portion of TSC2 is included in this duplication. Heterozygous loss of function variants in TSC2 are associated with tuberous sclerosis-2 and heterozygous loss of function variants in PKD1 are associated with adult type 1 polycystic kidney disease. ABCA3 is associated with autsomal recessive pulmonary surfactant metabolism dysfunction, and TBC1D24 is associated with several autosomal recessive conditions including early infantile epileptic encephalopathy, familial infantile myoclonic epilepsy, autosomal recessive deaness, and DOOR syndrome. Slightly larger duplications have been reported in DECIPHER in an individual with a kidney abnormality and mild intellectual disability (Case 263885) and in the general population in a single individual (chr16:2124547-2679656). No smaller overlapping duplications have been reported.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677978	SCV000804133	pathogenic	not provided	2018-03-19	criteria provided, single submitter	provider interpretation	This 13.9 Mb duplication from cytogenetic band 20p12.2 to 20q11.21 was determined to be present in the form of a supernumerary marker chromosome in an 8 year old male with a history of syndactyly of the toes, speech delay, developmental delay, nystagmus, and spontaneous pneumothorax. In particular, this result likely is indicative of a ring chromosome. This supernumerary chromosome was identifid in 88% of cells. Ring chromosomes of a similar size have been reported in databases in and in the literature (http://ssmc-tl.com/sSMC.html; Daber et al. 2012; Kitsiou-Tzeli et al. 2009; Guediche et al. 2010). Reported phenotypes of individuals with supernumerary marker chromosome are highly variable with unaffected individuals, growth retardation, atrial septal defect, facial dysmorphism, and developmental delay (Daber et al. 2012; Guediche et al. 2010; Kitsiou-Tzeli et al. 2009).
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677979	SCV000804134	uncertain significance	not provided	2018-03-19	criteria provided, single submitter	provider interpretation	This 82 kilobase duplication was identified in a patient with a history of autism spectrum disorder and global developmental delay. The duplication includes only the NDP gene. Loss of function of the NDP is associated with Norrie disease and exudative vitreoretinopathy, features of which include blindness in infancy, progressive hearing loss, developmental delays, intellectual disability, and psychosis. Females may rarely have some clinical manifestations. The impact of duplications of the NDP gene are unclear. This region is not known to vary in the general population. The patient's mother was found to carry this same duplication.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677980	SCV000804135	uncertain significance	not provided	2018-03-27	criteria provided, single submitter	provider interpretation	This 960 kilobase duplication was identified in a patient with a history of macrocephaly, dysmorphic features, atrial septal defect, agenesis of the corpus callosum, seizures, feeding disorder and global developmental delays. Parental testing confirmed this duplication was maternally inherited. This patient's mother has a reported history of anxiety, depression, and a mild learning disability. The duplication includes a portion of the CTNND2 gene, a gene that has been suggested to play a role in severity of intellectual disability in cri-du-chat syndrome. The impact of a partial duplication of this gene is unclear. Partial duplications have been reported in association with schizophrenia and in an individual with cerebral palsy (Vrijenhock et al. 2008; McMichael et al. 2014).
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677981	SCV000804136	uncertain significance	not provided	2018-03-22	criteria provided, single submitter	provider interpretation	This 1.1 Mb duplication within Xq12 was identified in a patient with a history of autism spectrum disorder and expressive speech delay. The duplication includes the EDA2R and AR genes. Smaller duplications within this region have been identified in individuals with intellectual disability (Madrigal et al. 2007; DECIPHER Case 249562). This duplication was identified in this patient's mother who has a reported history of a learning disability. A 15q11.2 deletion was also identified in this patient and his mother.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677982	SCV000804137	uncertain significance	not provided	2018-03-22	criteria provided, single submitter	provider interpretation	This 431 kilobase duplication was identified in a female patient with a history of developmental delay, eczema, and a receptive-expressive language disorder. This duplication was inherited from the patient's mother who reportedly has a history of learning difficulties and anxiety. This duplication includes 13 genes. Of those genes, only STK13 has been associated with a clinical condition. Specifically, STK13 is associated with autosomal recessive spermatogenic failure in males. The relevance of a duplication of this, or any of the other included genes, is unknown. Smaller, overlapping duplications in this region have been reported in DECHIPER in an individual with macrocephaly, hydrocephalus, and intellectual disability (Case 288189), an individual with inappropriate behavior and intellectual disability (Case 288524), and an individual with intellectual disability and psychosis (Case 290429). Smaller, overlapping duplications have also been reported in controls (Cooper et al. 2011).
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677983	SCV000804138	uncertain significance	not provided	2018-03-22	criteria provided, single submitter	provider interpretation	This 804 kilobase deletion was identified in a patient with speech delay , hypotonia, disruptive behaviors, learning disorder and dysmorphic features. The deletion includes seven genes, none of which have been associated with clinical disorders. The deletion was not identified in the patient's mother. His father has not undergone testing to date.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677984	SCV000804139	uncertain significance	not provided	2018-03-22	criteria provided, single submitter	provider interpretation	This 184 kilobase duplication was identified in a male with global developmental delay, microcephaly, autism spectrum disorder, hearing impairment, idiopathic toe walking, and dysmorphic features. The duplication includes 6 genes, only one of which, NSDHL, has been associated with a clinical condition. The effect of a duplication of this gene, or the others included, is unclear. The patient's mother was found to also carry this duplication. His mother does not have a reported history of neurodevelopmental concerns. The patient also underwent whole exome sequencing and was found to carry two variants of uncertain significance.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677985	SCV000804140	likely pathogenic	Dilated cardiomyopathy 1G	2017-12-04	criteria provided, single submitter	provider interpretation	This deletion was identified in a patient with a history of intellectual disability, autism spectrum disorder, and insomnia. A mitochondrial disorder has previously been suspected. The deletion includes a portion of the TTN and PLEKHA3 genes. PLEKHA3 has not been associated with a known condition at this time. TTN, however, is expressed in the skeletal and cardiac muscles and has been associated with several conditions including isolated cardiomyopathies, limb-girdle muscular dystrophy, proximal myopathy with early respiratory involvement, Salih myopathy, and Tibial muscular dystrophy. The deletion includes exons 229-313 of the TTN gene. This deletion includes the A and M bands of the protein and this particular deletion has not been reported previously. Deletions and loss of function variants in TTN that impact the A and M bands, such as the deletion found in this patient, are associated with isolated cardiomyopathies. 18-25% of dilated cardiomyopathies have been associated with such TTN variants. Deletions such as this have also been detected in healthy individuals (Herman et al. 2012). This could be due to reduced penetrance, however. The variant was also detected in the patient's mother who does not have a reported history of cardiomyopathy.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677987	SCV000804142	uncertain significance	not provided	2018-02-01	criteria provided, single submitter	provider interpretation	This 468 kilobase deletion was identified in a male with a history of mild intellectual disability and autism spectrum disorder. The deletion includes four genes, two of which (FANF and ANO5) are associated with a clinical disorder via autosomal recessive or dominant negative mechanisms.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677988	SCV000804143	uncertain significance	not provided	2018-03-22	criteria provided, single submitter	provider interpretation	This deletion was identified in a patient with a history of developmental delay, learning disorder, articulation disorder, stereotypic movements, and ADHD. The deletion overlaps with the Williams-Beuren critical region but does not include the ELN gene. The effect of this deletion is unclear. The patient also carries a 22q11.21 duplication and both copy number variants were found to be paternally inherited.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677989	SCV000804144	uncertain significance	not provided	2018-03-22	criteria provided, single submitter	provider interpretation	This 625 kilobase duplication was identified in an individual with a history autism and global developmental delay/intellectual disability. This duplication includes 15 genes, none of which are known to be triplosensitive at this time. This duplication was also identified in the patient's mother who reportedly has a history of speech and learning delays, asthma, and reflux.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677990	SCV000804145	uncertain significance	not provided	2018-03-22	criteria provided, single submitter	provider interpretation	This 98 kilobase duplication was identified in a patient with a history of learning disability, large stature, and overgrowth. The duplication includes ANKRD11 and SPG7 genes. These genes are associated with autosomal dominant KBG syndrome and spastic paraplegia type 7, respectively, but the effect of a duplication involving these genes is unclear. Copy number variation in this region has been reported in the general population. The duplication was detected in the patient's mother who does not have a reported history of neurodevelopmental concerns and is of typical stature. Additional genetic testing, including whole exome sequencing, has been performed and has not yieled an explanation for the patient's phenotype.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677991	SCV000804146	uncertain significance	not provided	2018-03-27	criteria provided, single submitter	provider interpretation	This duplication was identified in a 5 year old female with autism spectrum disorder and speech delay. The duplication was also found to be maternally inherited. Nonsense variants and deletions of SHOX have been reported in individuals with idiopathic short stature and Leri-Weill dyschondrosteosis (Huber et al. 2001; Niesler et al. 2002; Rappold et al. 2002). Partial or complete duplications of SHOX and/or its enhancer regions have also been reported in patients with these conditions (Thomas et al. 2009; Benito-Sanz et al. 2011). Tall stature has also been reported with duplications. This patient and her mother are of typical height. Whole exome sequencing also identified a variant of uncertain significance in this patient.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677992	SCV000804147	uncertain significance	not provided	2018-03-27	criteria provided, single submitter	provider interpretation	This 421 kilobase duplication was identified in a female with a history of short stature, ADHD, developmental language disorder, and borderline delays in visual-motor/problem-solving adaptive skills. Similar duplications that involve the ARX gene have been reported in males in the literature. Two males had developmental delay and intellectual disability while two others had typical intelligence, causing the authors to postulate that another genetic varaint explained or contributed to the two patients' neurodevelopmental phenotype (Popoviel et al. 2014). A likely pathogenic 22q11.21 atypical deletion was also identified in this patient.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677993	SCV000804148	likely pathogenic	not provided	2018-03-27	criteria provided, single submitter	provider interpretation	This 412 kilobase deletion was identified in an 11 year old patient with a history of intellectual disability, autism spectrum disorder, amblyopia, and congenital pes planus. Copy number variants of Xq28 have been associated with intellectual disability in males. Females in the literature have been reportedly asymptomatic due to skewed X-inactivation. X-inactivation studies for this patient demonstrated completely skewed X-inactivation (100:0). Similar deletions have been reported in the literature and are thought to be embryonic lethal in males (El-Hattab 2011; El-Hattab 2015). A likely benign 19p13.2 duplication was also identified, and parental testing indicated that the Xq28 deletion was maternally inherited. This patient's mother has a history of 3 miscarriages. Given the skewed X-inactivation in this patient, this deletion does not explain her neurodevelopmental phenotype. The deletion is likely associated with the mother's increased risk for miscarriage.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677994	SCV000804149	pathogenic	not provided	2018-03-27	criteria provided, single submitter	provider interpretation	This 2.6 Mb deletion was identified in a 10 year old male with a history of autism spectrum disorder, intellectual disability, and ADHD. Overlapping deletions of 15q24.1q24.2 have been identified in individuals with developmental delay, intellectual disability, dysmorphic features, hypotonia, digital anomalies, joint laxity and genital anomalies (Mefford et al. 2012; El-Hattab et al 2009; Van Esch et al. 2009). In the literature, deletions were de novo in each case. Parental follow-up testing has not been completed for this family to date.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677995	SCV000804150	uncertain significance	not provided	2018-03-27	criteria provided, single submitter	provider interpretation	This 1.6 Mb deletion was identified in a 16 year old male with a history of migraines, autism spectrum disoder, and anxiety. Maternal inheritance has been ruled out, but paternal testing has not been completed to date. A pathogenic 16p11.2 duplication was also identified in this patient.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677996	SCV000804151	uncertain significance	not provided	2018-04-03	criteria provided, single submitter	provider interpretation	This 41 kilobase deletion was identified in a 15 year old with a history of mild intellectual disability, speech and language disorder, and ADHD. The deletion includes a portion of the TPRX1 gene and the entire CRX gene. Deletions and loss of function variants in CRX have been associated with Leber congenital amaurosis 7, cone-rod dystrophy 2, and late-onset retinitis pigmentosa. Aside from a history of strabismus, the patient does not have a history of vision concerns. This deletion was determined to be maternally inherited. The patient's mother does not have a reported history of vision concerns.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677997	SCV000804152	uncertain significance	not provided	2018-04-03	criteria provided, single submitter	provider interpretation	This 156 kilobase duplication was identified in a 7 year old with a history of intellectual disability, autism spectrum disorder, pica, hyperkinesis, sleep disturbance, and polyuria. The duplication was found to be maternally inherited. The duplicated region includes a portion of the UPRT and ZDHHC15 genes. A loss of function variant in ZDHHC15 has been reported in an individual with intellectual disability (Manosouri et al. 2015), but the impact of a duplication of this variant is unclear.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677998	SCV000804153	pathogenic	not provided	2018-04-03	criteria provided, single submitter	provider interpretation	This approximately 2.2 Mb deletion was identified in a 13 year old female with a history of autism spectrum disorder, intellectual disability, and disruptive behavior. The deleted region includes 4 genes, including FOXP2. Loss of function FOXP2 variants are associated with speech and language disorders (Watkins et al 2002; Laffin et al. 2012; Fedorenko et al. 2016). Parental testing has not been completed to date.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000677999	SCV000804154	uncertain significance	not provided	2018-04-03	criteria provided, single submitter	provider interpretation	This 323 kilobase duplication was identified in a male with a history of obesity, acanthosis nigricans, mixed receptive-expressive language disorder, motor stereotypy. The duplication includes 15 genes, but none are known to be triplosensitive.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678000	SCV000804155	uncertain significance	Mitochondrial complex I deficiency	2018-03-28	criteria provided, single submitter	provider interpretation	This deletion was identified in a 6 year old female with microcephaly, history of developmental delays, Duane's syndrome, and alopecia. Parental testing was not completed. This deletion includes 10 genes including, STRN3, CPR33, ARGHAP5, NUBPL, and APA4S1. NUBPL sequencing and del/dup was negative for any additional changes in this gene. Individuals with deletions of NUBPL are typically asymptomatic carriers for complex 1 defiencicy. The clinical significance of this deletion is unknown.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678001	SCV000804156	uncertain significance	not provided	2018-03-28	criteria provided, single submitter	provider interpretation	This duplication was identified in a 4 year old female with global developmental delay, mild dysmorphic features, and esotropia. Parental testing was not completed. This deletion included a portion of the gene AUTS2. Additionally, a variant of uncertain significance in the LRRC7 gene was identified through whole exome sequencing. The clinical significance of this duplication remains unclear at this time.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678002	SCV000804157	uncertain significance	not provided	2018-03-28	criteria provided, single submitter	provider interpretation	This duplication was identified in a 9 year old male with language disorder, mild intellectual disability, mild hypotonia, disruptive behavior, sleep problems, and a history of global developmental delay. Parental testing was not completed. This duplication includes ten genes, three of which are associated with known clinical disorders; LRRK2, CNTN1, and PRICKLE1. The clinical significance of this duplication remains unclear at this time.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678003	SCV000804158	uncertain significance	not provided	2018-03-28	criteria provided, single submitter	provider interpretation	This duplication was identified in a 8 year old male with autism spectrum disorder, ADHD, and unspecified cognitive abilities. Parental testing was not completed. This duplication includes a portion of two genes, FSCN2 and RAAP100. The clinical consequences of a partial duplication of FSCN2 and FAAP100 remain unclear at this time.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678004	SCV000804159	uncertain significance	Autism	2018-03-28	criteria provided, single submitter	provider interpretation	This deletion was identified in a 13 year old male with autism spectrum disorder, intellectual disability, bipolar disorder, conduct disorder, periventricular leukomalacia, and asthma. Parental testing was not completed. This deletion includes a portion of CNTN4. Disruptions of CNTN4 have been reported in individuals with autism spectrum disorders, individuals with 3p- syndrome, and unaffected parents. It is not clear whether this deletion is related to the patient's neurodevelopmental history.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678005	SCV000804160	likely pathogenic	Autosomal recessive juvenile Parkinson disease 2	2018-03-01	criteria provided, single submitter	provider interpretation	This deletion was identified in a 3 year old male with bilateral intra-abdominal testicle, hypertelorism, conductive hearing loss, exotropia, global developmental delay, echogenic kidneys, abnormality of gait, and hyperkinesis. Parental testing was not completed. This deletion includes a portion of PARK2. Individuals with deletions of PARK2 are typically asymptomatic carriers for juvenile onset Parkinson Disease. There is a maternal family history of Parkinson Disease that onset before 30 years of age. This deletion does not explain the findings in this patient.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678006	SCV000804161	uncertain significance	not provided	2018-03-28	criteria provided, single submitter	provider interpretation	This deletion was identified in a 18 year old female with autism spectrum disorder, ADHD, and epilepsy. Parental testing was not completed. This deletion includes a portion of TMEM132C and the entirity of TMEM132B, SLC15A4, and GLT1D1, none of which are associated with a known clinical disorder at present. The clinical significance of this deletion remains unclear at this time.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678007	SCV000804162	uncertain significance	Landau-Kleffner syndrome	2018-03-28	criteria provided, single submitter	provider interpretation	This duplication was identified in a 4 year old male with macrocephaly, speech delay, autism spectrum disorder, large ears, and developmental delays, and was maternally inherited. Patient's mother has a history of anxiety, with a family history of depression, learning disabilities, and seizures. This duplication includes a portion of GRIN2A, which is associated with focal epilepsy and speech disorder with or without intellectual disability for heterozygous variants. However the clinical signifiance of this duplication is not known at this time. A maternally inherited variant of uncertain significance in the TB1X gene was also identified through whole exome sequencing.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678008	SCV000804163	uncertain significance	not provided	2018-03-30	criteria provided, single submitter	provider interpretation	This deletion was identified in a 10 year old female with nonintractable epilepsy with simple partial seizures, short stature, intellectual disability, and MRI brain abnormalities, and was maternally inherited. Patient's mother has a history of bipolar disorder and depression. This deletion contains 13 genes, including six OMIM genes: PTPN12, MAGI2, GNAI1, GNAT3, CD36, and SEMA3C. Individuals with varaints in CD36 are typically asymptomatic carriers for platelet glycoprotein IV deficiency. The clinical significance of this deletion beyond carrier status remains unclear at this time.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678009	SCV000804164	uncertain significance	not provided	2018-03-30	criteria provided, single submitter	provider interpretation	This duplication was identified in a 3 year old male with global developmental delays and a mixed receptive-expressive language disorder, and was found to be paternally inherited. Proband's father is reportedly unaffected, with no history of developmental delays. This duplication includes a portion of CBX7 and RPL3 genes, and the entirety of PDGFB. The clinical significance of a duplication of these genes is not currently known.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678010	SCV000804165	uncertain significance	Autism	2018-03-30	criteria provided, single submitter	provider interpretation	This deletion was identified in a 7 year old male with developmental speech disorder, disruptive behavior disorder, hypermetropia, constipation, ADHD, dysmorphic features, and a history of failure to thrive. Parental testing was not completed. This deletion includes a portion of CNTN4 and is within the larger distal 3p deletion syndrome region. CNTN4 is a candidate gene for autism spectrum disorders. The clinical significance of this deletion remains unclear at this time.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678011	SCV000804166	uncertain significance	Acrodysostosis 2 with or without hormone resistance	2018-03-30	criteria provided, single submitter	provider interpretation	This deletion was identified in a 10 year old male with autism spectrum disorder, macrocephaly, some hyperpigmented patches, some joint hypermobility, and anxiety. This deletion was also identified in the proband's twin brother who is similarly affected, but parental testing was not completed. This deletion includes three genes, including PDE4D , and is within the region for the much larger 5q12.1 deletion syndrome. The clinical significance of a deletion of these genes is not currently known.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678012	SCV000804167	likely pathogenic	not provided	2018-03-30	criteria provided, single submitter	provider interpretation	This duplication was identified in a 11 year old male with intellectual disability, autism spectrum disorder, ADHD, and a seizure disorder. Parental testing was not completed. This duplication includes 18 OMIM genes and 31 other genes. Identical duplications have not been reported, though overlapping duplications have been noted in DECIPHER in individuals with autism, intellectual disability, seizures, and dysmorphic features. Due to the size of this duplication, it is likely the explanation for this patient's presentation.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678013	SCV000804168	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2018-03-30	criteria provided, single submitter	provider interpretation	This deletion was identified in a 4 year old male with global developmental delays, macrocephaly, and craniosynostosis. Parental testing was not completed and there was a strong maternal family history of breast and ovarian cancer. This deletion includes BRCA2 and explains this family history, but is likely non-contributory to the proband's medical and developmental history.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678015	SCV000804170	pathogenic	Intellectual disability, autosomal recessive 7	2018-03-30	criteria provided, single submitter	provider interpretation	This homozygous deletion was identified in a 6 year old male with global developmental delays, short stature, chiari malformation type I, exotropia, and microcephaly. Microarray showed 5-6% homozygosity. Analysis of a maternal sample confirmed she is a heterozygous carrier for this deletion. This deletion includes at least exons 2-6 of TUSC3, which is associated with an autosomal recessive form of intellectual disability. This deletion explains the neurodevelopmental phenotype of this patient.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678016	SCV000804171	uncertain significance	Pigmented nodular adrenocortical disease, primary, 2	2018-03-30	criteria provided, single submitter	provider interpretation	This duplication was identified in a 9 year old male with history of global developmental delay, unspecified intellectual disability, ADHD, and esotropia. This patient also has a 15q11.2 deletion that is a known recurrent deletion associated with neurodevelopmental phenotypes and is believed to be the cause of this patient's symptoms. Parental testing was not completed for either variant, though there is a maternal family history for the 15q11.2 deletion. This duplication involves a portion of PDE11A. The clinical significance of the duplication of a portion of this gene is unclear at this time.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678017	SCV000804172	uncertain significance	not provided	2018-03-30	criteria provided, single submitter	provider interpretation	This deletion was identified in a 19 year old female with mild intellectual disability, ADHD, anxiety, and hyperphagia, and was found to be de novo. This patient has had normal whole exome sequencing. This deletion includes no genes that are associated with a known clinical phenotype at present. It is unclear at this time if this deletion is related to the patient's neurodevelopmental history.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678018	SCV000804173	uncertain significance	SIN3A-related intellectual disability syndrome due to a point mutation	2018-03-30	criteria provided, single submitter	provider interpretation	This duplication was identified in a 12 year old male with autism spectrum disorder, dysmorphic features, ADHD, a patent foramen ovale, and intellectual disability. Parental testing was not completed. This duplication includes 10 genes, including SIN3A. This duplication is within the 15q24 region, and similar duplications have been reported in patients with a similar phenotype to the recurrent deletion. The clinical significance of this duplication remains unclear.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678019	SCV000804174	uncertain significance	not provided	2018-03-30	criteria provided, single submitter	provider interpretation	This deletion was identified in a 8 year old male with autism spectrum disorder, ADHD, and obesity. Parental testing was not completed. This deletion contains the non-coding exon 1 of RBFOX1. Deletions within RBFOX1 have conflicting reports of clinical significance ranging from causing epilepsy and autism spectrum disorders to being normal variation. The clinical significance of the deletion of a portion of this gene is remains unclear.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678021	SCV000804176	pathogenic	not provided	2018-04-02	criteria provided, single submitter	provider interpretation	This deletion was identified in a 16 year old male with intellectual disability, seizure disorder, irritability, submucosal cleft palate, microcephaly, short stature, sleep disturbances, and Emery-Driefuss muscular dystrophy. Parental testing was not completed. This region contains at least 36 genes and was also identified on a karyotype. A 16p13.11 intragenic deletion of ABCC6 was also identified through array and a FHL1 likely pathogenic variant identified through a HCM gene panel. Due to its size, this deletion is believed to explain this patient's neurodevelopmental history in combination with his FHL1 mutation.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678022	SCV000804177	uncertain significance	not provided	2018-04-12	criteria provided, single submitter	provider interpretation	This duplication was identified in a 5 year old male with microcephaly, dysmorphic features (large ears, close set eyes, pointed chin), behavioral concerns, pica, myopia, astigmatism, and was found to be maternally inherited. This patient's mother has a history of learning problems and a bicornuate uterus, and a family history of ADHD, special education needs, schizophrenia, depression, deafness, and substance abuse. This duplication includes 18 genes, including MYO9B, CPAMD8, and GTPBP3. The clinical significance of the duplication of these genes remains unclear at this time.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678023	SCV000804178	pathogenic	Pitt-Hopkins-like syndrome 2	2018-04-12	criteria provided, single submitter	provider interpretation	This deletion was identified in a 17 year old male with autism spectrum disorder, intellectual disability, ADHD, aggression, constipation, and weight loss. Parental testing was not completed. This deletion includes a portion of NRXN1, and similar other deletions are have been reported in individuals with autism, intellectual disability, ADHD, schizophrenia, and/or seizures. Biallelic mutations in NRXN1 are associated with Pitt-Hopkins-like syndrome 2. Of note this patient does not have hyperbreathing, developmental regression, or facial dysmorphism. This deletion appears to explain the patient's medical history.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678024	SCV000804179	uncertain significance	Autosomal dominant nonsyndromic hearing loss 56	2018-04-12	criteria provided, single submitter	provider interpretation	This duplication was identified in a 13 year old male with learning disabilities, ADHD, articulation disorder, and mild dysmorphic features, and was maternally inherited. The patient's mother has a history of depression, anxiety, and five first trimester miscarriages. This duplication includes the entirity of TNC and DEC1, and a portion of PAPPA and TNFSF8. There is no family history of hearing loss. The clinical significance of carrying three copies of these genes is unclear at this time.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678025	SCV000804180	uncertain significance	Hypertrophic cardiomyopathy 16	2018-04-12	criteria provided, single submitter	provider interpretation	This duplication was identified in a 10 year old male with intellectual disability, macrocephaly, autism spectrum disorder, hyperkinesis, sleep disturbances, and hypodontia. Parental testing was not completed. This duplication includes the gene MYOZ2, which is associated with hypertrophic cardiomyopathy. There is one overlapping duplication reported in the literature that includes two additional genes in a patient with Cantu syndrome. The clinical significance of this duplication remains unclear at this time.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678026	SCV000804181	uncertain significance	Usher syndrome type 2A; Retinitis pigmentosa 39	2018-04-12	criteria provided, single submitter	provider interpretation	This duplication was identified in a 9 year old male with autism spectrum disorder, and a history of ADHD and developmental delays. Parental testing was not completed. This duplication includes two genes, KCTD3 and USH2A. Of note this patient is negative for hearing loss or retinitis pigmentosa. The clinical significance of this duplication remain unclear at this time.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678027	SCV000804182	uncertain significance	Charcot-Marie-Tooth disease axonal type 2K	2018-04-13	criteria provided, single submitter	provider interpretation	This deletion was identified in a 3 year old female with receptive-expressive language disorder, premature birth, hypotonia, poor feeding, posteriorly rotated ears, and up-slanting palpebral fissures, and is maternally inherited. This deletion includes six genes, including TMEM70, GDAP1, and JPH1. Individuals with single variants in TMEM70 are typically asymptomatic carriers for mitochondrial complex V deficiency. GADP1 and JPH1 have been described to cause an autosomal dominant Charcot-Marie-Tooth disease type 2K with muscle weakness and atrophy. Patient's mother reportedly has similar facial features and short stature, though no muscle concerns reported. The clinical significance of this deletion remains unclear at this time.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678029	SCV000804184	uncertain significance	not provided	2018-04-13	criteria provided, single submitter	provider interpretation	This duplication was identified in a 7 year old female with short stature, macrocephaly, intellectual disability, global developmental delays, midface hypoplasia, high forehead, periorbital fullness, thick eyebrows, broad nasal root, low nasal bridge, up-turned nasal tip, short philtrum, full lips, wide mouth, pointed chin, decreased motor strength, joint hyperflexibility, increased lordosis, hyperextensible joints, flat feet, and was found to be maternally inherited. This patient's mother has anxiety, asthma, required learning supports, and had a heart murmur. Mother and maternal grandmother reportedly had a history of infertility. This duplicated region contains six regions, including CDHR1, RGR, and a portion of CCSER2. The clinical significance of carrying three copies of these genes is unclear at this time. A second maternally inherited variant was identified through chromosomal microarray, a 1q32.3 deletion of uncertain significance.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678030	SCV000804185	uncertain significance	not provided	2018-04-13	criteria provided, single submitter	provider interpretation	This duplication was identified in a 3 year old female with autism spectrum disorder, overgrowth, macrocephaly, fine motor delay and speech delay, and was maternally inherited. This patient's mother has average cognitive abilities and has anxiety, depression, and OCD. This duplication includes a portion of VCX3A and VCX2, and the entirety of HDHD1, STS, VCX, and PNPLA4. Identical duplications in this region have been reported with conflicting reported pathogenicity (benign-pathogenic) in individuals with features including developmental delay, seizures, autism spectrum disorder, and intellectual disability. The clinical significance of three copies of these genes remains unclear at this time.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678031	SCV000804186	uncertain significance	not provided	2018-04-13	criteria provided, single submitter	provider interpretation	This deletion was identified in a 9 year old male with intellectual disability, gross motor delay, infantile benign external hydrocephaly, ADHD, overweight, and sleep difficulties, and was paternally inherited. This patient's father has bipolar and intellectual disability. This deletion includes ADARB2 and a portion of WDR37. Neither of these genes is associated with a known clinical disorder at present. Overlapping deletions have been seen in individuals with developmental delay or dysmorphic features, with some including the gene ZMYND11 that is known to cause intellectual disability. The clinical significance of this deletion remains unclear at this time.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678033	SCV000804188	uncertain significance	not provided	2018-04-16	criteria provided, single submitter	provider interpretation	This duplication was identified in a 5 year old male with overgrowth, developmental regression, speech delay, autism spectrum disorder, with history of an EEG with paroxysmal discharges that were considered epileptiform, and a brain MRI that noted scattered foci of T2 hyperintensity in the cerebral white matter bilaterally. Parental testing was not completed. This duplication contains seven genes, including GCSH, and a portion of an eighth gene. The clinical significance of three copies of these genes remains unclear at this time.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678034	SCV000804189	pathogenic	Spinocerebellar ataxia type 15/16	2018-04-16	criteria provided, single submitter	provider interpretation	This deletion was identified in a 4 year old male with global developmental delays, seizures, hypermetropia of both eyes, amblyopia of right eye, hemangioma, dysmorphic features (triangular facies, broad forehead, prominent crus, almond shaped eyes, thick eyebrows, hypoplastic alae, prominent nasal tip, thin lips, narrow palate, pointed chin, decreased motor strength), partial agenesis of the corpus callosum, and prenatal exposure to cigarettes. Parental testing was not completed for the patient's father and the patient's mother tested negative. This deletion contains two genes SUMF1 and SETMAR, and a portion of ITPR1. Heterozygous carriers of SUMF1 variants are most often asymptomatic carriers for multiple sulfatase deficiency. Deletions of ITPF1 have been shown to cause spinocerebellar ataxia type 15. Microarray also identified a likely pathogenic duplication at 13q13.3.
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System	RCV000678035	SCV000804190	likely pathogenic	not provided	2018-04-16	criteria provided, single submitter	provider interpretation	This duplication was identified in a 4 year old male with global developmental delays, seizures, hypermetropia of both eyes, amblyopia of right eye, hemangioma, dysmorphic features (triangular facies, broad forehead, prominent crus, almond shaped eyes, thick eyebrows, hypoplastic alae, prominent nasal tip, thin lips, narrow palate, pointed chin, decreased motor strength), partial agenesis of the corpus callosum, and prenatal exposure to cigarettes. Parental testing was not completed for the patient's father and the patient's mother tested negative. This duplication contains two genes, MIR17HG and GPC5, and a portion of GPC6. Similar duplications including MIR17HG and a portion of GPC5 have been reported in two individuals: one with postaxial polydactyly, overgrowth, autistic features, and dysmorphic features and was inherited from a similarly affected mother, and in a patient with developmental delay, autism spectrum disorder, short stature, macrocephaly, brachydactyly, clinodactyly, and dysmorphic features that was also identified in a parent and sibling with similar features. This duplication likely contributes to the phenotype of this patient. Microarray in our patient also identified a pathogenic deletion at 3q26.1, which is associated with spinocerebellar ataxia type 15.
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000754994	SCV000804194	pathogenic	Short-rib thoracic dysplasia 19 with or without polydactyly	2018-07-03	criteria provided, single submitter	research
Daryl Scott Lab, Baylor College of Medicine	RCV000681464	SCV000808912	pathogenic	Neurodevelopmental disorder with or without anomalies of the brain, eye, or heart	2017-09-12	criteria provided, single submitter	clinical testing
Medical Genetics Lab, Policlinico S. Orsola.Malpighi	RCV000681666	SCV000809058	uncertain significance	Intellectual disability, mild	2018-09-27	criteria provided, single submitter	clinical testing	This is a homozygous deletion that involves only the BTBD9 gene, identified in a patient with mild intellectual disability, microcephaly, mild dismorphism. Parents are healthy, second-degree cousins of Italian origin, and are heterozygous carriers of the deletion. A healthy brother is also heterozygous. BTBD9 has not been currently associated to any monogenic disorder in humans, but it is expressed in brain and is a good candidate for neurodevelopmental disorders.
Undiagnosed Diseases Network, NIH	RCV000708570	SCV000837689	pathogenic	Cornelia de Lange syndrome 5	2018-03-16	criteria provided, single submitter	clinical testing
Undiagnosed Diseases Network, NIH	RCV000708593	SCV000837720	likely pathogenic	Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome	2018-01-04	criteria provided, single submitter	clinical testing
Genetics - Synnovis, NHS South East Genomic Laboratory Hub	RCV003232084	SCV000845782	pathogenic	Ectrodactyly	2018-10-31	criteria provided, single submitter	clinical testing	Duplications of this region are associated with split hand/foot malformation 3.
Genetics - Synnovis, NHS South East Genomic Laboratory Hub	RCV003232085	SCV000845790	pathogenic	Ectrodactyly		criteria provided, single submitter	clinical testing	Duplications of this region are associated with split hand/foot malformation 3.
Eurofins Ntd Llc (ga)	RCV000734617	SCV000862771	other	not provided	2018-08-06	criteria provided, single submitter	clinical testing
Undiagnosed Diseases Network, NIH	RCV000735205	SCV000863411	uncertain significance	Branched-chain keto acid dehydrogenase kinase deficiency	2018-03-16	criteria provided, single submitter	clinical testing
Undiagnosed Diseases Network, NIH	RCV000735209	SCV000863416	likely pathogenic	TAX1BP3-related arrhythmogenic right ventricular cardiomyopathy	2018-11-27	criteria provided, single submitter	clinical testing	A hemizygous c.233T>C (p.M78T) variant in the TAX1BP3 gene was detected in three brothers (14yo male, 20yo male, and male that died suddently at age 17) with similar symptoms. Exome sequencing showed that all three brothers are hemizygous, the mother is heterozygous, and the father is negative for this change. Concurrent array analysis revealed a heterozygous copy number loss of approximately 238 Kb in size (genomic position chr17:3394299- 3632836) in all three brothers. This large deletion encompasses the entire TAX1BP3 gene. SNP arrays detected this deletion as heterozygous in all three brothers and the father. The mother is negative for the deletion. Therefore, the 238 Kb deletion and the c.233T>C (p.M78T) variant are located on two chromosomes (in trans configuration). We believe the combination of the missense variant and deletion in trans is likely pathogenic.
Undiagnosed Diseases Network, NIH	RCV000735211	SCV000863419	pathogenic	Developmental and epileptic encephalopathy, 4	2017-10-23	criteria provided, single submitter	clinical testing
Undiagnosed Diseases Network, NIH	RCV000735212	SCV000863420	pathogenic	Deafness-infertility syndrome	2017-11-14	criteria provided, single submitter	clinical testing
Undiagnosed Diseases Network, NIH	RCV000735214	SCV000863422	pathogenic	Charcot-Marie-Tooth disease, type IA	2018-06-26	criteria provided, single submitter	clinical testing	1.4Mb pathogenic copy number gain on chromosome 17 at 17p12. Detected by chromosomal microarray.
Undiagnosed Diseases Network, NIH	RCV000735229	SCV000863438	pathogenic	Wieacker-Wolff syndrome	2017-06-15	criteria provided, single submitter	clinical testing	95 kb deletion includes coding exon 1 which explains X-linked pathogenicity. Carrier females may have mild features of Wieacker-Wolff syndrome compared to hemizygous males.
Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano	RCV000785663	SCV000863549	uncertain significance	Silver Russell Syndrome-related disorder	2018-12-06	criteria provided, single submitter	research
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000735898	SCV000864010	uncertain significance	Trichorhinophalangeal dysplasia type I	2018-12-17	criteria provided, single submitter	research
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000735899	SCV000864011	uncertain significance	Trichorhinophalangeal dysplasia type I	2018-12-17	criteria provided, single submitter	research
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000735900	SCV000864012	pathogenic	Trichorhinophalangeal dysplasia type I	2018-12-17	criteria provided, single submitter	research
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000735901	SCV000864013	pathogenic	Hypoparathyroidism, deafness, renal disease syndrome	2018-12-17	criteria provided, single submitter	research
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000735904	SCV000864016	uncertain significance	Cerebellar dysfunction with variable cognitive and behavioral abnormalities	2018-12-17	criteria provided, single submitter	research
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000735905	SCV000864017	benign	Cerebellar dysfunction with variable cognitive and behavioral abnormalities	2018-12-17	criteria provided, single submitter	research
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000735906	SCV000864018	uncertain significance	Cerebellar dysfunction with variable cognitive and behavioral abnormalities	2018-12-17	criteria provided, single submitter	research
Raymond Lab, University of Cambridge	RCV000850220	SCV000897737	pathogenic	Intellectual disability	2019-02-13	criteria provided, single submitter	research
Biochemistry Laboratory of CDMU, Chengde Medical University	RCV000768460	SCV000899223	likely pathogenic	not provided		criteria provided, single submitter	case-control
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000852264	SCV000900011	likely pathogenic	Hereditary factor IX deficiency disease	2019-02-01	criteria provided, single submitter	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000852266	SCV000900014	likely pathogenic	Hereditary factor X deficiency disease	2019-02-01	criteria provided, single submitter	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000852267	SCV000900015	likely pathogenic	Abnormal bleeding	2019-02-01	criteria provided, single submitter	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000852258	SCV000900022	likely pathogenic	11q partial monosomy syndrome	2019-02-01	criteria provided, single submitter	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000852269	SCV000900025	likely pathogenic	Thrombocytopenia	2019-02-01	criteria provided, single submitter	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000852261	SCV000900027	likely pathogenic	Hereditary antithrombin deficiency	2019-02-01	criteria provided, single submitter	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000852271	SCV000900030	likely pathogenic	Deep venous thrombosis	2019-02-01	criteria provided, single submitter	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000852272	SCV000900031	likely pathogenic	Protein S deficiency disease	2019-02-01	criteria provided, single submitter	research
Undiagnosed Diseases Network, NIH	RCV000786772	SCV000924629	likely pathogenic	1p13.3 deletion syndrome	2019-06-06	criteria provided, single submitter	clinical testing	Both loss- and gain-of-function mutations in the KCNA2 gene cause early infantile epileptic encephalopathy-32 (EIEE-32; # 616366) (Allen, et al. Epilepsia. 2016 Jan;57(1):e12-7.). EIEE causes severe epilepsy with variable types of seizures, and neurological deficits, including intellectual disability, and delay of psychomotor and language development. Ataxia, tremor, and myoclonus have also been associated with EIEE. The onset of seizures has been reported to typically occur at less than five years of age and may remit later in childhood, however, one individual with a deletion involving all of the KCNA2 gene was reported to have onset of generalized tonic-clonic seizures at the age of 14 along with intellectual disability (Lal, et al. PLoS Genet. 2015 May 7;11(5):e1005226.) Within this deletion, two other genes, SLC25A24 and GNAI3 have been associated with autosomal dominant disorders. Mutations in SLC25A24 have been associated with Gorlin-Chaudhry-Moss syndrome and Fontaine progeroid syndrome (FPS, OMIM #612289), which have overlapping clinical features. Several studies suggest that the SLC25A24 mutations for these indiviudals induce a gain of function. Mutations of GNAI3 have been identified in patients with auriculocondylar syndrome-1 (ARCND1 or ACS, OMIM #602483), and it is thought that ACS is not caused by GNAI3 haploinsufficiency. For both of these disorders, whole gene deletions would not be expected to result in the same mechanism or clinical features of these disorders. Additionally, six genes are associated with autosomal recessive conditions, for which this deletion likely infers a carrier status. Chudley-McCullough syndrome (CMCS; #604213) is caused by homozygous or compound heterozygous mutation in the GPSM2 gene, while autosomal recessive mental retardation-60 (MRT60; # 617432) and autosomal recessive mental retardation-48 (MRT48; #616269) are caused by mutations in the TAF13 and SLC6A17 genes, respectively. Pontocerebellar hypoplasia type 9 (PCH9; #615809) is caused by mutations in both copies of the AMPD2 gene and frontonasal dysplasia-1 (FND1; OMIM #136760), are caused by mutations in both copies of the ALX3 gene.
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787370	SCV000926332	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787371	SCV000926333	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787372	SCV000926334	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787374	SCV000926336	likely pathogenic	Skeletal dysplasia	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787375	SCV000926337	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787376	SCV000926338	pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787377	SCV000926339	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787378	SCV000926340	uncertain significance	Tooth agenesis; Kidney disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787379	SCV000926341	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787381	SCV000926343	pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787382	SCV000926344	pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787383	SCV000926345	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787384	SCV000926346	likely pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787385	SCV000926347	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787386	SCV000926348	likely pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787387	SCV000926349	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787388	SCV000926350	uncertain significance	Growth abnormality	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787389	SCV000926351	uncertain significance	Growth abnormality	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787390	SCV000926352	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787391	SCV000926353	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787392	SCV000926354	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787395	SCV000926357	pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787396	SCV000926358	pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787397	SCV000926359	pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787399	SCV000926361	likely pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787400	SCV000926362	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787401	SCV000926363	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787402	SCV000926364	pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787403	SCV000926365	pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787404	SCV000926366	pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787405	SCV000926367	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787406	SCV000926368	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787407	SCV000926369	likely pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787409	SCV000926371	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787410	SCV000926372	uncertain significance	Growth abnormality	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787411	SCV000926373	likely pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787412	SCV000926374	pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787413	SCV000926375	pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787414	SCV000926376	uncertain significance	Growth abnormality	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787415	SCV000926377	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787416	SCV000926378	likely pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787417	SCV000926379	uncertain significance	Encephalopathy	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787418	SCV000926380	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787419	SCV000926381	uncertain significance	Epilepsy	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787420	SCV000926382	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787421	SCV000926383	uncertain significance	Internal malformations	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787422	SCV000926384	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787425	SCV000926387	likely pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787426	SCV000926388	pathogenic	Epilepsy	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787428	SCV000926390	pathogenic	Epilepsy	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787429	SCV000926391	uncertain significance	Skeletal dysplasia	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787430	SCV000926392	uncertain significance	Growth abnormality	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787435	SCV000926397	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787436	SCV000926398	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787437	SCV000926399	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787439	SCV000926401	pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787440	SCV000926402	pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787441	SCV000926403	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787442	SCV000926404	likely pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787443	SCV000926405	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787444	SCV000926406	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787445	SCV000926407	likely pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787447	SCV000926409	likely pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787448	SCV000926410	likely pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787449	SCV000926411	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787450	SCV000926412	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787451	SCV000926413	uncertain significance	Arthrogryphosis	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787452	SCV000926414	pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787453	SCV000926415	uncertain significance	Premature ovarian failure	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787454	SCV000926416	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787455	SCV000926417	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787457	SCV000926419	likely pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787461	SCV000926423	uncertain significance	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787463	SCV000926425	uncertain significance	Growth abnormality	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787464	SCV000926426	pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787465	SCV000926427	pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787466	SCV000926428	pathogenic	Neurodevelopmental disorder	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787468	SCV000926430	likely pathogenic	Muscle dystrophy	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787469	SCV000926431	uncertain significance	Internal malformations	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787470	SCV000926432	likely pathogenic	Muscle dystrophy	2019-04-09	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000787472	SCV000926434	pathogenic	Skeletal dysplasia	2019-04-09	criteria provided, single submitter	clinical testing
Undiagnosed Diseases Network, NIH	RCV000754630	SCV000930559	pathogenic	Kilquist syndrome	2019-01-01	criteria provided, single submitter	clinical testing	Homozygous deletion of SLC12A2 due to uniparental paternal isodisomy. Deletion from intron 1 to the beginning of exon 7 (chr5:127441491â€ 127471419) including an inversion of 34 base pairs (chr5:127441491â€127471419delins34). As a carrier, the father shows no symptoms of Kilquist syndrome. This family has been reported in PMID: 30740830.
Undiagnosed Diseases Network, NIH	RCV000791288	SCV000930566	likely pathogenic	Kleefstra syndrome 2	2017-12-15	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000824954	SCV000965989	pathogenic	Intellectual disability, severe	2016-01-01	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000824957	SCV000965998	pathogenic	Marfan syndrome	2016-01-01	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000825024	SCV000966219	pathogenic	Obesity due to leptin receptor gene deficiency	2018-07-17	criteria provided, single submitter	clinical testing	Observed as a homozygote.
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000825026	SCV000966221	pathogenic	15q11q13 microduplication syndrome	2018-10-16	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000825598	SCV000966941	likely pathogenic	Lynch syndrome	2018-04-27	criteria provided, single submitter	clinical testing	This MSH2 variant is a deletion encompassing exons 8 to 15, though it should be noted that its exact breakpoints cannot be determined due to limitations of the testing methodology. This multi-exon deletion has been reported in 1 individual with Lynch syndrome and 1 individual referred for hereditary cancel panel testi ng at a diagnostic laboratory (Liu 1994, Susswein 2015) and has also been report ed by another clinical laboratory in ClinVar (Variation ID# 417806). Deletions w ithin exons 8 to 15 as well as larger deletions spanning these exons have been r eported in multiple individuals with colorectal cancer in the Human Gene Mutatio n Database (HGMD: Stenson 2017). This deletion is predicted to result in a prema ture stop codon in the last exon on the MSH2 gene (exon 16), and while it is mor e likely to escape nonsense mediated decay, it is expected to result in a trunca ted protein where approximately half of the MSH2 coding sequence is removed. In summary, although additional studies are required to fully establish its clinica l significance, this variant is likely pathogenic. ACMG/AMP Criteria applied: PV S1_strong, PM2.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000825957	SCV000967442	uncertain significance	not specified	2018-10-29	criteria provided, single submitter	clinical testing	This deletion encompasses MIR96; however, please note that the exact breakpoints of this deletion could not be determined by this assay. Several multi-gene dele tions encompassing MIR96 have been reported in individuals with developmental de lay and other features in the DECIPHER database, however hearing loss was not re ported for any of these individuals and the deletions reported impacted >200 gen es (https://decipher.sanger.ac.uk). Recurrent smaller deletions encompassing onl y the miR-183/182/96 cluster and the 3? end of an adjacent gene (NRF1) have been reported in dbVar in several control population studies with one study reportin g a MAF of 0.3% (12/4052 alleles) in healthy controls (Shaikh 2009), which sugge st that the loss of MIR96 is not likely to be disease causing. However, due to t he technical limitation of this assay in detecting the breakpoints and length of this deletion, the impact of this deletion on neighboring disease-relevant gene s cannot be determined. In summary, although loss of MIR96 is not expected to be related to hearing loss, due to uncertainty regarding the size and breakpoints of the deletion, the clinical significance of this deletion is uncertain. ACMG/A MP criteria applied: none.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000826027	SCV000967517	uncertain significance	not specified	2018-04-12	criteria provided, single submitter	clinical testing	The c.(?_-15)_(1947_?)dup variant in RAF1 is a duplication of the coding exons: exons 2-17. The exact breakpoints of this gain cannot be determined by this meth od, and exon 1 is not included in the test as it is non-coding. Gains of the RAF 1 gene, including large CNVs that include RAF1 and other genes, have been report ed in several individuals with variable phenotypes as well as in healthy control s. Large CNVs encompassing RAF1 and additional genes been reported in one indivi dual with TOF and two individuals with varying phenotypes and severity, one of w hich was inherited from an unaffected father (Silversides 2012, Luo 2012, Lissew ski 2015). Whole gene gains of RAF1 have also been reported in 3 individuals in Decipher (http://decipher.sanger.ac.uk/) with ID and other phenotypes, two of wh ich were inherited from an unaffected parent. Large CNVs encompassing RAF1 and a dditional genes has been reported as uncertain in ClinVar, in ten individuals in the Database of Genomic Variants (DGV, http://dgv.tcag.ca), and in 3/41234 tota l chromosomes in Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org). In summary, the clinical significance of this partial gain of the RAF1 gen e is uncertain.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000826068	SCV000967562	uncertain significance	not specified	2018-03-23	criteria provided, single submitter	clinical testing	The duplication of exons 192-244 in TTN has not been previously reported in indi viduals with cardiomyopathy. It is unknown if this duplication is in tandem, wit h the possibility of altering protein expression/function, or was inserted in a different locus, which may not impact the protein. A similar duplication, involv ing exons 193-244, was identified by our laboratory in one individual with DCM. A larger intragenic duplication involving this region was identified in one cont rol sample (Kidd 2008). In summary, the clinical significance of this duplicatio n is uncertain.
Academic Department of Medical Genetics, University of Cambridge	RCV000850066	SCV000992232	uncertain significance	Hereditary cancer-predisposing syndrome	2018-01-26	criteria provided, single submitter	research
Academic Department of Medical Genetics, University of Cambridge	RCV000850067	SCV000992233	uncertain significance	Hereditary cancer-predisposing syndrome	2018-01-26	criteria provided, single submitter	research
Academic Department of Medical Genetics, University of Cambridge	RCV000850068	SCV000992234	uncertain significance	Hereditary cancer-predisposing syndrome	2018-01-26	criteria provided, single submitter	research
Academic Department of Medical Genetics, University of Cambridge	RCV000850149	SCV000992322	uncertain significance	Hereditary cancer-predisposing syndrome	2018-01-26	criteria provided, single submitter	research
Academic Department of Medical Genetics, University of Cambridge	RCV000850150	SCV000992323	pathogenic	Hereditary leiomyomatosis and renal cell cancer; Hereditary cancer-predisposing syndrome	2018-01-26	criteria provided, single submitter	research	Observed in an individual with phenotype specific for variants in one of the deted genes
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000851176	SCV000993410	likely pathogenic	Marfanoid habitus and intellectual disability		criteria provided, single submitter	research
GeneDx	RCV000984805	SCV000998934	likely pathogenic	not provided	2018-02-26	criteria provided, single submitter	clinical testing	The c.5419_5420insAlu variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is the result of an Alu mobile insertion element interrupting coding sequence in exon 30 and is predicted to cause loss of normal protein function. Mobile insertion elements, including retrotransposon-mediated events such as Alu inserts, are estimated to account for 1 in 600 disease causing variants (Kazazian et al., 1999). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
GeneDx	RCV001004047	SCV000998935	pathogenic	not provided	2019-06-03	criteria provided, single submitter	clinical testing	The c.1276_1277insAlu variant in the EFTUD2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This individual harbors a mobile insertion element that consists of Alu sequence that is approximately 300 base pairs in length and is predicted to cause loss of normal protein function. Mobile insertion elements, including retrotransposon-mediated events such as Alu inserts, are estimated to account for 1 in 600 disease causing variants (Kazazian et al., 1999). Therefore, we interpret c.1276_1277insAlu as a pathogenic variant.
GeneDx	RCV000984894	SCV000998936	pathogenic	not provided	2018-04-25	criteria provided, single submitter	clinical testing	The c.426_427insAlu variant in the ETFB gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This fetus harbors a mobile insertion element that consists of Alu sequence that is approximately 300 base pairs in length and is predicted to cause loss of normal protein function. Mobile insertion elements, including retrotransposon-mediated events such as Alu inserts, are estimated to account for 1 in 600 disease causing variants (Kazazian et al., 2000). Therefore, we interpret c.426_427insAlu as a pathogenic variant.
GeneDx	RCV000984895	SCV000998937	pathogenic	not provided	2019-06-21	criteria provided, single submitter	clinical testing	Founder mutation in the Ashkenazi Jewish population which is observed in homozygous state in multiple unrelated patients in published literature (Tucker et al., 2011; Berzoykin et al., 2015), and not observed in homozygous state in controls. Mobile insertion element that consists of Alu sequence that is 353 base pairs in length, also described as c.1284_1285ins353 or c.428_429ins353 in the literature. Published functional studies demonstrate a damaging effect (loss of retina-specific isoform of MAK) (Tucker et al., 2011). Not observed in large population cohorts (Database of Genomic Variants). We interpret this as a Pathogenic Variant.
GeneDx	RCV000984896	SCV000998938	pathogenic	not provided	2018-02-01	criteria provided, single submitter	clinical testing	The c.1926_1927insAlu variant in the NSD1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This individual harbors a mobile insertion element that consists of Alu sequence that is approximately 300 base pairs in length and is predicted to cause loss of normal protein function. Mobile insertion elements, including retrotransposon-mediated events such as Alu inserts, are estimated to account for 1 in 600 disease causing variants (Kazazian et al., 2000). Additionally, Alu-mediated recombination leading to microdeletions of the NSD1 gene has been previously described in individuals with Sotos syndrome (Mochizuki et al., 2008). Therefore, we interpret c.1926_1927insAlu as a pathogenic variant.
GeneDx	RCV000985237	SCV000999045	pathogenic	not provided	2018-06-12	criteria provided, single submitter	clinical testing	The c.431_432insAlu variant in the OFD1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This individual harbors a mobile insertion element that consists of Alu sequence that is approximately 300 base pairs in length and is predicted to cause loss of normal protein function. Mobile insertion elements, including retrotransposon-mediated events such as Alu inserts, are estimated to account for 1 in 600 disease causing variants (Kazazian et al., 1999). Therefore, we interpret c.431_432insAlu as a pathogenic variant.
GeneDx	RCV000985238	SCV000999047	likely pathogenic	not provided	2018-12-10	criteria provided, single submitter	clinical testing	The c.131+2_c.131+3insAlu variant in the SLC26A3 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. This individual harbors a mobile insertion element that consists of Alu sequence that is approximately 300 base pairs in length and is predicted to cause loss of normal protein function. Mobile insertion elements, including retrotransposon-mediated events such as Alu inserts, are estimated to account for 1 in 600 disease causing variants (Kazazian et al., 2000). Therefore, we interpret c.131+2_c.131+3insAlu as a likely pathogenic variant.
GeneDx	RCV000985239	SCV000999048	pathogenic	not provided	2019-03-13	criteria provided, single submitter	clinical testing	The c.8932_8933insAlu variant in the USH2A gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This individual harbors a mobile insertion element that consists of Alu sequence that is approximately 300 base pairs in length and is predicted to cause loss of normal protein function. Mobile insertion elements, including retrotransposon-mediated events such as Alu inserts, are estimated to account for 1 in 600 disease causing variants (Kazazian, 1999). Therefore, we interpret c.8932_8933insAlu as a pathogenic variant.
GeneDx	RCV000985240	SCV000999049	pathogenic	not provided	2018-11-15	criteria provided, single submitter	clinical testing	The c.1600_1601insAlu variant in the ZEB2 gene has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. This variant is the result of an Alu mobile insertion element interrupting coding sequence in exon 8 and is predicted to cause loss of normal protein function. Mobile insertion elements, including retrotransposon-mediated events such as Alu inserts, are estimated to account for 1 in 600 disease causing variants (Kazazian et al., 1999). Therefore, this variant is considered a pathogenic variant.
GeneDx	RCV000985241	SCV000999050	pathogenic	not provided	2019-08-22	criteria provided, single submitter	clinical testing	Has not been previously reported as pathogenic or benign to our knowledge. Not observed in large population cohorts (MacDonald et al., 2014). This variant is the result of an Alu mobile insertion element interrupting coding sequence in exon 30 and is predicted to cause loss of normal protein function. Mobile insertion elements, including retrotransposon-mediated events such as Alu inserts, are estimated to account for 1 in 600 disease causing variants (Kazazian et al., 1999). We interpret this as a Pathogenic Variant.
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine	RCV001171631	SCV000999934	pathogenic	Intellectual disability	2019-11-18	criteria provided, single submitter	research	The variant is a deletion overlapping coding exons of CRHR1, SPPL2C, MAPT, STH genes, and exons 3-15 of the KANSL1 gene. Deletions overlapping KANSL1 gene have been shown to cause Koolen-de Vries syndrome, a clinically heterogeneous disorder characterized by hypotonia, developmental delay, moderate intellectual disability, and characteristic facial dysmorphism (PMID: 22544363, 26306646). This variant was identified in an adult undergoing exome sequencing due to a history of intellectual disability and developmental delay. For these reasons, this variant has been classified as Pathogenic.
Cavalleri Lab, Royal College of Surgeons in Ireland	RCV001031017	SCV001160792	pathogenic	Proximal 16p11.2 microdeletion syndrome	2019-12-11	criteria provided, single submitter	research
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV001005017	SCV001164581	likely pathogenic	Duchenne muscular dystrophy	2018-12-03	criteria provided, single submitter	research	The heteroygous deletion variant in DMD was identified by our study in one female with Duchenne Muscular Dystrophy. Manifesting female carriers of DMD have been previously reported (Mercieret al., 2013). This deletion variant in DMD has not been previously reported in individuals with Duchenne Muscular Dystrophy and was absent from large population studies. This variant is a deletion of Exon 1 and 2 and is predicted to impact the protein, including the start codon. Loss of function of the DMD gene is an established disease mechanism in autosomal recessive Duchenne Muscular Dystrophy. A splice site variant affecting Exon 2 has been reported pathogenic for Duchenne Muscular Dystrophy in ClinVar by Invitae and EGL Genetic Diagnostics, suggesting that Exon 2 is important for protein function (Variation ID: 283346). In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic.
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001027727	SCV001190163	pathogenic	Common variable immunodeficiency	2019-01-01	criteria provided, single submitter	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001027728	SCV001190164	pathogenic	Common variable immunodeficiency	2019-01-01	criteria provided, single submitter	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001027643	SCV001190215	likely pathogenic	Inherited Immunodeficiency Diseases	2019-01-01	criteria provided, single submitter	research
Central Laboratory, The First Hospital of Lanzhou University	RCV001200047	SCV001190325	pathogenic	22q13.3 interstitial deletion	2020-03-09	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089808	SCV001245295	pathogenic	Hereditary breast ovarian cancer syndrome	2019-02-04	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 11 of the BRCA2 gene (c.6003_6004insAlu), causing a frameshift at codon 2002 (p.Glu2002fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with BRCA2-related disease. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018), and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089809	SCV001245296	pathogenic	Hereditary breast ovarian cancer syndrome	2019-12-11	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 11 of the BRCA2 gene (c.2844_2845insAlu), causing a frameshift at codon 948 (p.Val948fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with BRCA2-related disease. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this allele has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089810	SCV001245297	likely pathogenic	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2019-06-06	criteria provided, single submitter	clinical testing	This sequence change is an Alu-mediated insertion in exon 326 of the TTN mRNA (c.85261_85262insAlu), causing a frameshift at codon 28421 (p.Ile28421fs). The exact size and sequence of the insertion cannot be determined by the current assay. While this insertion is not anticipated to result in nonsense mediated decay, it is expected to create a truncated TTN protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TTN-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). This variant is located in the A band of TTN (PMID: 25589632). Truncating variants in this region are significantly overrepresented in patients affected with dilated cardiomyopathy (PMID: 25589632). Truncating variants in this region have also been reported in individuals affected with autosomal recessive centronuclear myopathy (PMID: 23975875). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089811	SCV001245298	pathogenic	not provided	2019-06-10	criteria provided, single submitter	clinical testing	This sequence change is an Alu-mediated insertion in exon 22 of the PHEX mRNA (c.2193_2194insAlu), causing a frameshift at codon 731 (p.Phe731fs). The exact size and sequence of the insertion cannot be determined by the current assay. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 19 amino acids of the PHEX protein. This variant is not present in population databases (ExAC no frequency). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the C-terminus of the PHEX protein. Other variant(s) that disrupt this region (p.Arg747*) have been determined to be pathogenic (PMID: 9199930, 9768674). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089812	SCV001245299	pathogenic	Neurofibromatosis, type 1	2019-04-07	criteria provided, single submitter	clinical testing	This sequence change is an Alu-mediated insertion in exon 2 of the NF1 mRNA (c.195_196insAlu), causing a frameshift at codon 65 (p.Val65fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NF1-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). Loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538) and other Alu-mediated insertions in NF1 have been reported to be de novo in the literature (PMID: 1719426). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089813	SCV001245300	pathogenic	Ataxia-telangiectasia syndrome	2019-07-05	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 5 of the ATM gene (c.364_365delinsAlu), causing a frameshift at codon 122 (p.Asnfs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089815	SCV001245302	uncertain significance	Mitochondrial trifunctional protein deficiency; Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency	2019-09-05	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in intron 2 of the HADHA gene (c.110-25_110-24insAlu). It does not directly change the encoded amino acid sequence of the HADHA protein and it is unknown how it will affect the protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with HADHA-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089816	SCV001245303	pathogenic	Neurofibromatosis, type 1	2019-05-03	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 32 of the NF1 gene (c.4320_4321insAlu), causing a frameshift at codon p.Met1440 (p.Met1440fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NF1-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in NF1 are known to be pathogenic (PMID: 10712197, 23913538). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089817	SCV001245304	pathogenic	Familial cancer of breast	2019-06-07	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 13 of the CHEK2 gene (c.1406_1407insAlu), causing a frameshift at codon 469 (p.Val469fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with CHEK2-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089818	SCV001245305	pathogenic	Retinitis pigmentosa 12; Leber congenital amaurosis 8	2019-12-22	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 6 of the CRB1 gene (c.1454_1455insAlu), causing a frameshift at codon 486 (p.Leu486fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CRB1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in CRB1 are known to be pathogenic (PMID: 10508521, 22065545, 23379534, 25412400, 26957898, 28041643, 29391521). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089819	SCV001245306	pathogenic	Ataxia-telangiectasia syndrome	2019-12-15	criteria provided, single submitter	clinical testing	This sequence change is an Alu-mediated insertion in exon 19 of the ATM mRNA (c.2852_2853insAlu), causing a frameshift at codon 951 (p.Leu951fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ATM-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089820	SCV001245307	pathogenic	Hereditary breast ovarian cancer syndrome	2019-02-16	criteria provided, single submitter	clinical testing	This sequence change is an Alu-mediated insertion in exon 16 of the BRCA2 mRNA (c.7665_7666insAlu), causing a frameshift at codon 2556 (p.Asn2556fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). Although this variant has not been reported in the literature, loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584) and other Alu-mediated insertions in BRCA2 have been reported in the literature (PMID: 20232141). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089821	SCV001245308	pathogenic	Ataxia-telangiectasia syndrome	2019-12-11	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 20 of the ATM gene (c.3055_3056insAlu), causing a frameshift at codon 1019 (p.Leu1019fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with ATM-related disease. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089823	SCV001245310	pathogenic	PTEN hamartoma tumor syndrome	2019-05-14	criteria provided, single submitter	clinical testing	This sequence change is an Alu-mediated insertion in exon 5 of the PTEN mRNA (c.432_433insAlu), causing a frameshift at codon 145 (p.Phe145fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). Although this variant has not been reported in the literature, loss-of-function variants in PTEN are known to be pathogenic (PMID: 9467011, 21194675) and similar Alu-mediated insertions in PTEN have been reported in individuals affected with Cowden syndrome (PMID: 28513612). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089824	SCV001245311	pathogenic	Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma	2019-12-15	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 3 of the SDHB gene (c.250_251insAlu), causing a frameshift at codon 84 (p.Asp84fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with SDHB-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in SDHB are known to be pathogenic (PMID: 19454582, 19802898). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089825	SCV001245312	pathogenic	Hereditary breast ovarian cancer syndrome	2019-05-28	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 11 of the BRCA2 gene (c.3083_3084insAlu), causing a frameshift at codon 1028 (p.Lys1028fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with BRCA2-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089829	SCV001245316	uncertain significance	Tumor predisposition syndrome 3	2019-01-17	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 10 of the POT1 gene (c.717_718insAlu), causing a frameshift at codon 240 (p.Arg240fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with POT1-related conditions. The current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in POT1 cause disease. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089830	SCV001245317	pathogenic	not provided	2019-02-11	criteria provided, single submitter	clinical testing	This sequence change is an Alu-mediated insertion in exon 33 of the VPS13A mRNA (c.3525_3526insAlu), causing a frameshift at codon 1176 (p.Gln1176fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with VPS13A-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). Loss-of-function variants in VPS13A are known to be pathogenic (PMID: 12404112, 21598378). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089831	SCV001245318	pathogenic	Fabry disease	2019-09-03	criteria provided, single submitter	clinical testing	This sequence change is an Alu-mediated insertion in exon 5 of the GLA mRNA (c.744_745insAlu), causing a frameshift at codon 249 (p.Asn249fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). Although this variant has not been reported in the literature, loss-of-function variants in GLA are known to be pathogenic (PMID: 10666480, 12175777). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089832	SCV001245319	pathogenic	Cystic fibrosis	2019-07-28	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 24 of the CFTR gene (c.3955_3956insAlu), causing a frameshift at codon 1319 (p.Ala1319fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089833	SCV001245320	pathogenic	Duchenne muscular dystrophy	2019-09-09	criteria provided, single submitter	clinical testing	This sequence change is an Alu-mediated insertion in exon 43 of the DMD mRNA (c.6220_6221insAlu), causing a premature translational stop signal (p.Leu2074_Met3685delinsArgSerIleAsnPheValAspMetGlnPro*). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DMD-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in DMD are known to be pathogenic (PMID: 16770791, 25007885). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089834	SCV001245321	pathogenic	Hereditary breast ovarian cancer syndrome	2019-09-24	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 11 of the BRCA2 gene (c.3082_3083insAlu), causing a frameshift at codon 1028 (p.Lys1028fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089835	SCV001245322	pathogenic	not provided	2019-10-17	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 4 of the RP1 gene (c.4052_4053insAlu), causing a frameshift at codon 1352 (p.Tyr1352Alafs9). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). A similar variant has been observed in individual(s) with autosomal recessive retinal disease (PMID: 30913292, 31253780). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. That variant is also known as c.4052_4053ins328 (p.Tyr1352Alafs9) in the literature. This variant disrupts the C-terminus of the RP1 protein. Many variants that disrupt this region have been reported in individuals with either autosomal dominant or autosomal recessive retinitis pigmentosa (PMID: 11527933, 19933189, 29425069, 30027431). Therefore, variants that disrupt this region are expected to be disease-causing. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to disrupt protein function (PMID: 19763152, 20307669, 22406018). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089836	SCV001245323	pathogenic	Ataxia-telangiectasia syndrome	2020-01-19	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 50 of the ATM gene (c.7388_7389insAlu), causing a frameshift at codon 2463 (p.Leu2463fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with ATM-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089839	SCV001245326	pathogenic	Hereditary nonpolyposis colorectal neoplasms	2019-08-30	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 11 of the PMS2 gene (c.1848_1849insAlu), causing a frameshift at codon 617 (p.Pro617fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). Although this variant has not been reported in the literature, loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089840	SCV001245327	pathogenic	Li-Fraumeni syndrome	2019-06-30	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 9 of the TP53 gene (c.970_971insAlu), causing a frameshift at codon 324 (p.Asp324fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with TP53-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in TP53 are known to be pathogenic (PMID: 20522432). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089842	SCV001245329	pathogenic	Alstrom syndrome	2019-12-13	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 20 of the ALMS1 gene (c.12184_12185insAlu), causing a frameshift at codon 4062 (p.Leu4062fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ALMS1-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in ALMS1 are known to be pathogenic (PMID: 17594715). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089843	SCV001245330	pathogenic	Hereditary nonpolyposis colorectal neoplasms	2019-11-04	criteria provided, single submitter	clinical testing	This sequence change is an Alu-mediated insertion in exon 12 of the MSH2 mRNA (c.1972_1973insAlu), causing a frameshift at codon 658 (p.Glu658fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). Although this variant has not been reported in the literature, loss-of-function variants in MSH2 are known to be pathogenic (PMID: 15849733, 24362816). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089844	SCV001245331	pathogenic	Familial cancer of breast	2019-12-19	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 9 of the CHEK2 gene (c.985_986insAlu), causing a frameshift at codon 329 (p.Tyr329fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with CHEK2-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in CHEK2 are known to be pathogenic (PMID: 21876083, 24713400). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089845	SCV001245332	pathogenic	not provided	2019-12-18	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 16 of the PHEX gene (c.1681_1682insAlu), causing a frameshift at codon 560 (p.Phe560fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PHEX-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in PHEX are known to be pathogenic (PMID: 9097956, 9106524, 19219621). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089846	SCV001245333	pathogenic	not provided	2020-01-03	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 9 of the MAK gene (c.1297_1298insAlu), causing a frameshift at codon 433 (p.Lys433fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. A similar Alu insertion has been observed in homozygosity in many individuals affected with autosomal recessive retinitis pigmentosa and may be a Jewish founder variant (PMID: 21825139, 25097241). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 21825139). Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in MAK are known to be pathogenic (PMID: 21148103, 21825139, 24938718, 29781741). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089847	SCV001245334	pathogenic	not provided	2019-12-24	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 4 of the RP1 gene (c.2321_2322insAlu), causing a frameshift at codon 774 (p.Leu774fs). The exact size and sequence of the insertion cannot be determined by the current assay. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1383 amino acids of the RP1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with autosomal dominant retinal disease (Invitae). This variant disrupts the C-terminus of the RP1 protein. Many variants that disrupt this region have been reported in individuals with either autosomal dominant or autosomal recessive retinitis pigmentosa (PMID: 11527933, 19933189, 29425069, 30027431). Therefore, variants that disrupt this region are expected to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089848	SCV001245335	pathogenic	Bardet-Biedl syndrome	2019-03-14	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ala406Glnfs*65) in the BBS1 gene. It is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with BBS1-related conditions. Loss-of-function variants in BBS1 are known to be pathogenic (PMID: 12118255). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089849	SCV001245336	pathogenic	Hereditary breast ovarian cancer syndrome	2019-10-07	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 10 of the BRCA1 gene (c.3950_3951insAlu), causing a frameshift at codon 1317 (p.Leu1317fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BRCA1-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in BRCA1 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089850	SCV001245337	likely pathogenic	Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J	2019-02-08	criteria provided, single submitter	clinical testing	This sequence change is an Alu-mediated insertion in exon 273 of the TTN mRNA (c.52063_52064insAlu), causing a frameshift at codon 17355. This creates a premature translational stop signal (p.His17355Argfs*17) and is expected to result in a disrupted protein product. This variant is found in the A-band of this gene. While this particular variant has not been reported in the literature, truncating variants in the A-band of TTN are significantly overrepresented in patients with dilated cardiomyopathy and are considered to be likely pathogenic for the disease (PMID: 25589632). For these reasons, this variant has been classified as Likely Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089851	SCV001245338	pathogenic	Fanconi anemia	2019-04-23	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 14 of the FANCM gene (c.4143_4144insAlu), causing a frameshift at codon 1382 (p.Asp1382fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. Similar retrotransposon insertions have not been reported in the literature in individuals with FANCM-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in FANCM are known to be pathogenic (PMID: 29895858, 30075111). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089852	SCV001245339	pathogenic	Birt-Hogg-Dube syndrome	2019-11-06	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 14 of the FLCN gene (c.1557_1558insAlu), causing a frameshift at codon 520 (p.Lys520fs). The exact size and sequence of the insertion cannot be determined by the current assay. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 78 amino acids of the FLCN protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with FLCN-related conditions. This variant disrupts the C-terminus of the FLCN protein. Other variant(s) that disrupt this region (p.Arg527*) have been determined to be pathogenic (PMID: 15852235, 17028174, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089853	SCV001245340	pathogenic	not provided	2019-10-30	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 4 of the RP1 gene (c.3352_3353insAlu), causing a frameshift at codon 1117 (p.Phe1117fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RP1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the C-terminus of the RP1 protein. Many variants that disrupt this region have been reported in individuals with either autosomal dominant or autosomal recessive retinitis pigmentosa (PMID: 11527933, 19933189, 29425069, 30027431). Therefore, variants that disrupt this region are expected to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089855	SCV001245342	pathogenic	Ataxia-telangiectasia syndrome	2019-11-11	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 23 of the ATM gene (c.3292_3293insAlu), causing a frameshift at codon 1097 (p.Phe1097fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with ATM-related conditions. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089856	SCV001245343	pathogenic	Hypertrophic cardiomyopathy	2019-08-09	criteria provided, single submitter	clinical testing	This sequence change is an Alu-mediated insertion in exon 33 of the MYBPC3 mRNA (c.3659_3660insAlu), causing a frameshift at codon 1220 (p.Asp1220fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. This variant has not been reported in the literature in individuals with MYBPC3-related disease. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). Loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089857	SCV001245344	pathogenic	Eichsfeld type congenital muscular dystrophy	2019-05-10	criteria provided, single submitter	clinical testing	This sequence change is an Alu-mediated insertion in exon 4 of the SELENON mRNA (c.487_488insAlu), causing a frameshift at codon 163 (p.Gln163fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018). While this particular variant has not been reported in the literature, loss of function variants in SELENON are known to be pathogenic (PMID: 21670436, 12192640). For these reasons, this variant has been classified as Pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001089858	SCV001245345	pathogenic	Hereditary breast ovarian cancer syndrome	2019-07-07	criteria provided, single submitter	clinical testing	This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 11 of the BRCA2 gene (c.5007_5008insAlu), causing a frameshift at codon 1670 (p.Ala1670fs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018), and loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). A retrotransposon insertion at this location in BRCA2 has been reported in individuals undergoing testing for hereditary breast and ovarian cancer (PMID: 29025590) For these reasons, this variant has been classified as Pathogenic.
Genetics and Genomics, Alberta Children's Hospital	RCV001095544	SCV001245472	likely pathogenic	Hiatus hernia; Expressive language delay; Microcephaly; Delayed gross motor development; Mild short stature; Delayed fine motor development	2020-05-04	criteria provided, single submitter	clinical testing	This duplication was classified as likely pathogenic due to segregation studies and its absence from controls.
Undiagnosed Diseases Network, NIH	RCV001090215	SCV001245610	pathogenic	PHIP-related behavioral problems-intellectual disability-obesity-dysmorphic features syndrome	2019-09-20	criteria provided, single submitter	clinical testing
Neurogenetics Research Program, University of Adelaide	RCV001194626	SCV001338856	pathogenic	Allan-Herndon-Dudley syndrome	2020-01-29	criteria provided, single submitter	research
Blueprint Genetics	RCV001250749	SCV001426168	pathogenic	Angelman syndrome	2017-11-24	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV001250750	SCV001426169	pathogenic	Angelman syndrome	2018-06-19	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV001250751	SCV001426170	pathogenic	Angelman syndrome	2018-11-02	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV001250752	SCV001426171	risk factor	Proximal 16p11.2 microdeletion syndrome	2017-12-08	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV001250753	SCV001426172	pathogenic	Mowat-Wilson syndrome	2018-03-22	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV001250754	SCV001426173	pathogenic	Chromosome 1p36 deletion syndrome	2018-05-09	criteria provided, single submitter	clinical testing
Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research	RCV001254217	SCV001430286	pathogenic	Autosomal dominant polycystic kidney disease	2019-01-01	criteria provided, single submitter	research
Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research	RCV001254247	SCV001430287	pathogenic	Autosomal dominant polycystic kidney disease	2019-01-01	criteria provided, single submitter	research
Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research	RCV001256004	SCV001430883	pathogenic	Autosomal dominant polycystic kidney disease	2019-01-01	criteria provided, single submitter	research
Laboratory of Medical Genetics, University of Torino	RCV001257570	SCV001433614	likely pathogenic	Intellectual disability, autosomal dominant 57	2020-09-24	criteria provided, single submitter	research	The deletion spans TLK2 and has been identified in a proband with intellectual disability and delayed motor development. The variant was de novo. The cells carrying the deletion show chromatin relaxation.
INGEBI, INGEBI / CONICET	RCV001257507	SCV001434335	pathogenic	Nonsyndromic genetic hearing loss	2020-08-31	criteria provided, single submitter	clinical testing	Based on ACMG/AMP guidelines and Hearing Loss Expert Panel specific criteria: the deletion (g.20797177_21105945del) known as del(GJB6-D13S1830) eliminates a 309-kb fragment including the first five exons (and a portion of the sixth exon) of GJB6 and the whole CRYL1 genes. It was demonstrated that CX26 and Cx30 can form heteromeric connexons and heterotypic gap-junction channels (PMID: 14681039). The GJB2+/- GJB6+/tm1Kwi double heterozygous mice have moderate hearing loss and a significantly reduced of endocochlear potential (PMID: 12917317, 28823936). In addition to this, functional studies in mice demonstrated that the GJB6tm1Kwi mouse is not only a GJB6 knockout but also decreases the transcription of the contiguous GJB2 gene (PMID: 19047647, 22098503). Furthermore, an independent GJB6 knock-out strain that carries a complete deletion of the GJB6 coding sequence, without inserted material, diminish the effect on GJB2 decrease expression (PMID:23303923 ). Therefore, this evidence supports the existence of a regulatory element within some part of the deletion among with the digenic pattern mode of inheritance proposed (PS3). The filter allele frequency of this variant is 0.02% from Genome Aggregation Database and Database of Genomic Variants (last update 01-04-2020 and 17-05-2020 respectively) meeting PM2_Supporting criteria. This variant was found to have a statistically higher prevalence in affected individuals over controls (PS4; PMID: 11807148). The del(GJB6-D13S1830) variant has been detected in trans with at least 4 GJB2 pathogenic variants applying to PM3_VeryStrong rule (PMID: 24158611, 11807148, 14571368). Therefore, this variant meets criteria to be classified as pathogenic for autosomal recessive non-syndromic hearing loss (PS3, PS4, PM2_Supporting, PM3_VeryStrong).
INGEBI, INGEBI / CONICET	RCV001257508	SCV001434336	pathogenic	Nonsyndromic genetic hearing loss	2020-08-31	criteria provided, single submitter	clinical testing	The deletion: del(GJB6-D13S1854) (g.20802727_21034768del) eliminates a 232-kb fragment including the first five exons of GJB6 and the last 4 exons of CRYL1 gene. It was demonstrated that CX26 and Cx30 can form heteromeric connexons and heterotypic gap-junction channels (PMID: 14681039). Besides, Gjb2+/- Gjb6+/tm1Kwi double heterozygous mice have moderate hearing loss and a significantly reduced endocochlear potential (PMID: 12917317, 28823936) In addition to this, functional studies in mice demonstrated that the Gjb6tm1Kwi mouse is not only a Gjb6 knockout but also decreases the transcription of the contiguous Gjb2 gene (PMID:19047647, 22098503). Furthermore, an independent Gjb6 knock-out strain that carries a complete deletion of the Gjb6 coding sequence, without inserted material, diminish the effect on GJB2 decrease expression (PMID:23303923 ). Therefore, these evidence support the existence of the regulatory element within some part of the deletion among with the digenic pattern mode of inheritance proposed. (PS3). This deletion is absent from Genome Aggregation Database and Database meeting PM2 rule. This variant was found to have a statistically higher prevalence in affected individuals over controls (PS4; PMID: 11807148). The del(GJB6-D13S1854) variant has been detected in trans with at least 4 pathogenic variants in GJB2 in hearing loss patients applying to PM3_VeryStrong rule (PMID: 15994881, 24158611). Therefore, this variant meets criteria to be classified as pathogenic for autosomal recessive non-syndromic hearing loss (PS3, PS4, PM3_S, PM2).
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV001260502	SCV001437523	uncertain significance	not provided	2019-11-05	criteria provided, single submitter	clinical testing	A deletion of approximately 1235.340 KB (chr14:22006109-23241448x1) located at 14q11.2 and encompassing 127 genes was detected in this individual. Deletions involving 14q11.2 have been previously reported in individuals with autism, developmental delay, intellectual disability, and seizures in DECIPHER. However, deletions involving 14q11.2 have also been observed in the Database of Genomic Variants and classified as benign in ClinVar. Based on the available evidence, this deletion is classified as a Variant of Uncertain Significance.
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV001260503	SCV001437524	pathogenic	not provided	2020-05-13	criteria provided, single submitter	clinical testing	A deletion of approximately 7.5 Mb (chr10:81585301-89101700x1) located at 10q22.3q23.2 was detected in this individual. This deletion encompasses 31 protein encoding genes of which 7 have been reported in OMIM with a disease-association (PMID: 19344873). Pathogenic deletions involving this region are associated with Chromosome 10q22.3-q23.2 deletion syndrome (MIM: #612242), and have been previously reported in patients with dysmorphic features, developmental delay, behavioral concerns, limb anomalies, and congenital heart defects (PMID: 28588438, 21248748, 20345475). The reported congenital heart defects are of variable severity and include: patent ductus arteriosus, atrioventricular septal defect, tetralogy of Fallot, pulmonic regurgitation, tricuspid regurgitation, and ventricular septal defect (PMID: 28588438). This variant has not been observed at a significant frequency in the Database of Genomic Variants and thus is presumed to be rare. This result was confirmed by orthogonal testing. Analysis of the parental samples showed that the mother is negative and the father is negative for this variant, indicating that the 7.5 Mb deletion likely occurred as a de novo event in the proband. Based on the available evidence, this deletion is classified as Pathogenic.
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV001260932	SCV001438021	pathogenic	not provided	2019-09-16	criteria provided, single submitter	clinical testing	A 12.9 MB deletion on chromosome 13 (chr13:102175801-115169858del) encompassing the CARKD gene was identified in this patient, in trans with a missense variant in CARKD c.1112C>T (p.Ser371Leu) that was classified as Likely Pathogenic. On the basis of this evidence, the 12.9 MB deletion was classified as Pathogenic.
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001262041	SCV001439419	pathogenic	Telangiectasia, hereditary hemorrhagic, type 1	2018-01-01	criteria provided, single submitter	research	PVS1+PM2+PP4
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001262047	SCV001439425	pathogenic	Telangiectasia, hereditary hemorrhagic, type 1	2018-01-01	criteria provided, single submitter	research	PVS1+PM2+PP4
Center for Statistical Genetics, Columbia University	RCV001261860	SCV001448212	pathogenic	Intellectual disability	2020-10-16	criteria provided, single submitter	research
Bertuch Lab, Baylor College of Medicine	RCV001523792	SCV001450739	pathogenic	Chromosome 16q22 deletion syndrome		criteria provided, single submitter	clinical testing	This structural variant results in whole gene deletion of CARMIL2, ACD, PARD6A, ENKD1, C16orf86, and GFOD2, as well as partial deletion of CTCF and RANBP10. When heterozygous, this chromosomal deletion resulted in chr16q22.1 microdeletion syndrome, with phenotypes of developmental delay, poor growth, facial dysmorphism, and hypotonia. Telomere lengths were found to be between the 1st and 10th centiles for age in the five lymphocyte populations, although similar to the lengths of the proband's parents who did not have the chromosomal deletion. Multiple CBCs obtained between the ages of 16 months and 4 years were normal.
Institute of Medical Molecular Genetics, University of Zurich	RCV001270921	SCV001451705	pathogenic	Congenital miosis	2020-12-21	criteria provided, single submitter	clinical testing
Center for Statistical Genetics, Columbia University	RCV001271073	SCV001451899	uncertain significance	Intellectual disability	2020-10-02	criteria provided, single submitter	clinical testing
Hadassah Hebrew University Medical Center	RCV001293248	SCV001468314	pathogenic	Harel-Yoon syndrome		criteria provided, single submitter	clinical testing
Hadassah Hebrew University Medical Center	RCV001293249	SCV001468315	pathogenic	Harel-Yoon syndrome		criteria provided, single submitter	clinical testing
Hadassah Hebrew University Medical Center	RCV001293250	SCV001468316	pathogenic	Harel-Yoon syndrome		criteria provided, single submitter	clinical testing
Hadassah Hebrew University Medical Center	RCV001293251	SCV001468317	pathogenic	Harel-Yoon syndrome		criteria provided, single submitter	clinical testing
New York Genome Center	RCV001281486	SCV001468794	uncertain significance	Seizure	2019-09-04	criteria provided, single submitter	clinical testing
New York Genome Center	RCV001281541	SCV001468850	uncertain significance	Heart, malformation of; Intellectual disability	2019-07-17	criteria provided, single submitter	clinical testing
Laboratory of Diagnosis and Therapy of Lysosomal Disorders, University of Padova	RCV001578513	SCV001547742	uncertain significance	Mucopolysaccharidosis, MPS-IV-A	2021-02-01	criteria provided, single submitter	research	Absent from gnomAD v2.1.1 (PM2_moderate)
Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University	RCV001391666	SCV001593290	pathogenic	Syndromic X-linked intellectual disability Lubs type	2021-05-13	criteria provided, single submitter	clinical testing
Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University	RCV001391667	SCV001593291	pathogenic	Deletion of short arm of chromosome 18	2021-05-13	criteria provided, single submitter	clinical testing
Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University	RCV001391668	SCV001593292	pathogenic	Developmental delay with variable intellectual impairment and behavioral abnormalities	2021-05-13	criteria provided, single submitter	clinical testing
Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University	RCV001391669	SCV001593293	pathogenic	not provided	2021-05-13	criteria provided, single submitter	clinical testing
Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University	RCV001391670	SCV001593294	pathogenic	Distal 10q deletion syndrome	2021-05-13	criteria provided, single submitter	clinical testing
Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University	RCV001391671	SCV001593295	pathogenic	Proximal 16p11.2 microdeletion syndrome	2021-05-13	criteria provided, single submitter	clinical testing
Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University	RCV001391672	SCV001593296	pathogenic	DiGeorge syndrome	2021-05-13	criteria provided, single submitter	clinical testing
Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University	RCV001391673	SCV001593297	pathogenic	Pelizaeus-Merzbacher disease; Hereditary spastic paraplegia 2	2021-05-13	criteria provided, single submitter	clinical testing
Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University	RCV001391674	SCV001593298	likely pathogenic	Chromosome 15q26-qter deletion syndrome	2021-05-13	criteria provided, single submitter	clinical testing
Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University	RCV001391675	SCV001593299	pathogenic	DiGeorge syndrome	2021-05-13	criteria provided, single submitter	clinical testing
Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University	RCV001391676	SCV001593300	likely pathogenic	Proximal 16p11.2 microdeletion syndrome	2021-05-13	criteria provided, single submitter	clinical testing
Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University	RCV001391677	SCV001593301	pathogenic	Distal monosomy 13q	2021-05-13	criteria provided, single submitter	clinical testing
Genetics and Prenatal Diagnosis Center, The First Affiliated Hospital of Zhengzhou University	RCV001391678	SCV001593302	likely pathogenic	not provided	2021-05-13	criteria provided, single submitter	clinical testing
Genetic Disease Research Branch / Genetics Development and Disease Section, National Human Genome Research Institute	RCV001420680	SCV001623011	pathogenic	Tyrosinase-positive oculocutaneous albinism	2021-02-01	criteria provided, single submitter	research	This represents a loss of function allele in OCA2 in a well described reccessive disease. ACMG: PVS1. PM4, PM3
Genetic Disease Research Branch / Genetics Development and Disease Section, National Human Genome Research Institute	RCV001420681	SCV001623012	pathogenic	Tyrosinase-positive oculocutaneous albinism	2021-02-01	criteria provided, single submitter	research
Mayo Clinic Laboratories, Mayo Clinic	RCV001449852	SCV001653249	pathogenic	Hypercholesterolemia, familial, 1	2019-04-25	criteria provided, single submitter	clinical testing	An in-frame duplication involving exons 2-6 of the LDLR gene.
Mayo Clinic Laboratories, Mayo Clinic	RCV001449853	SCV001653250	pathogenic	not provided	2020-09-24	criteria provided, single submitter	clinical testing	An in-frame deletion involving exons 3-4 of the LDLR gene.
Mayo Clinic Laboratories, Mayo Clinic	RCV001449854	SCV001653251	pathogenic	Hypercholesterolemia, familial, 1	2020-12-09	criteria provided, single submitter	clinical testing	An in-frame deletion involving exons 3-5 of the LDLR gene.
Mayo Clinic Laboratories, Mayo Clinic	RCV001449855	SCV001653252	pathogenic	Hypercholesterolemia, familial, 1	2019-09-18	criteria provided, single submitter	clinical testing	An in-frame deletion of exon 5 of the LDLR gene. Exon 5 of LDLR encodes LR6, one of the LDLR class A repeats/ligand binding domains. PS3, PS4, PM1, PM3, PM4
Mayo Clinic Laboratories, Mayo Clinic	RCV001449856	SCV001653253	pathogenic	Hypercholesterolemia, familial, 1	2019-08-30	criteria provided, single submitter	clinical testing	An out-of-frame deletion of exons 7-12 of the LDLR gene. PVS1, PM1, PM2
Mayo Clinic Laboratories, Mayo Clinic	RCV001449857	SCV001653254	pathogenic	Hypercholesterolemia, familial, 1	2019-11-21	criteria provided, single submitter	clinical testing	An in-frame deletion of exon 15 of the LDLR gene. PS4, PP1_Strong, PS3_Moderate, PM2, PM4
Mayo Clinic Laboratories, Mayo Clinic	RCV001449858	SCV001653255	uncertain significance	not provided	2019-06-14	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001449859	SCV001653256	uncertain significance	not provided	2021-03-24	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001449860	SCV001653257	pathogenic	Marfan syndrome	2020-04-23	criteria provided, single submitter	clinical testing	An in-frame deletion of exons 43-46 of the FBN1 gene. PVS1_Strong, PS3, PP4
Mayo Clinic Laboratories, Mayo Clinic	RCV001449861	SCV001653258	pathogenic	not provided	2020-10-07	criteria provided, single submitter	clinical testing	A deletion of exons 30-35 of the MYBPC3 gene. PVS1, PM1, PM2
Mayo Clinic Laboratories, Mayo Clinic	RCV001449862	SCV001653259	pathogenic	Telangiectasia, hereditary hemorrhagic, type 1	2019-05-09	criteria provided, single submitter	clinical testing	An out-of-frame duplication of exon 2 of the ENG gene.
Mayo Clinic Laboratories, Mayo Clinic	RCV001449863	SCV001653260	pathogenic	Telangiectasia, hereditary hemorrhagic, type 1	2021-03-11	criteria provided, single submitter	clinical testing	An out-of-frame deletion of exon 2 of the ENG gene. PVS1, PS4_moderate, PM2_supporting
Mayo Clinic Laboratories, Mayo Clinic	RCV001449864	SCV001653261	pathogenic	Telangiectasia, hereditary hemorrhagic, type 1	2019-06-25	criteria provided, single submitter	clinical testing	An in-frame deletion of exons 9-10 of the ENG gene.
Mayo Clinic Laboratories, Mayo Clinic	RCV001449865	SCV001653262	pathogenic	Telangiectasia, hereditary hemorrhagic, type 1	2020-05-15	criteria provided, single submitter	clinical testing	An in-frame deletion of exons 9-11 of the ENG gene. PVS1_Strong, PS4_moderate, PP5, PP4
Mayo Clinic Laboratories, Mayo Clinic	RCV001449866	SCV001653263	pathogenic	not provided	2020-07-30	criteria provided, single submitter	clinical testing	A whole gene deletion of the SLC2A1 gene. PVS1, PM2, PP4
Mayo Clinic Laboratories, Mayo Clinic	RCV001449867	SCV001653264	uncertain significance	not provided	2020-10-20	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001449868	SCV001653265	likely pathogenic	not provided	2020-10-20	criteria provided, single submitter	clinical testing	An out-of-frame deletion involving exon 2 of the NPRL3 gene. PVS1, PM2
Mayo Clinic Laboratories, Mayo Clinic	RCV001449869	SCV001653266	uncertain significance	not provided	2020-04-22	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001449870	SCV001653267	uncertain significance	not provided	2021-01-05	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001449871	SCV001653268	uncertain significance	not provided	2021-01-05	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001449872	SCV001653269	uncertain significance	not provided	2020-10-15	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001449873	SCV001653270	pathogenic	not provided	2021-02-14	criteria provided, single submitter	clinical testing	A whole gene deletion of the TSC2 gene. PVS1, PS4_moderate, PM2
Mayo Clinic Laboratories, Mayo Clinic	RCV001449874	SCV001653271	pathogenic	not provided	2019-06-18	criteria provided, single submitter	clinical testing	An out-of-frame deletion involving exons 8-9 of the CLN3 gene. PVS1, PS3, PS4, PM3
Mayo Clinic Laboratories, Mayo Clinic	RCV001449875	SCV001653272	pathogenic	not provided	2020-01-29	criteria provided, single submitter	clinical testing	A whole gene duplication of the PMP22 gene.
Mayo Clinic Laboratories, Mayo Clinic	RCV001449876	SCV001653273	pathogenic	not provided	2021-04-29	criteria provided, single submitter	clinical testing	A whole gene deletion of the PMP22 gene.
Mayo Clinic Laboratories, Mayo Clinic	RCV001449877	SCV001653274	likely pathogenic	not provided	2019-12-25	criteria provided, single submitter	clinical testing	A deletion involving exons 8-24 of the MAN2B1 gene.
Mayo Clinic Laboratories, Mayo Clinic	RCV001449878	SCV001653275	uncertain significance	not provided	2020-04-30	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001449879	SCV001653276	pathogenic	not provided	2019-12-26	criteria provided, single submitter	clinical testing	An out-of-frame duplication involving exons 61-62 of the DMD gene.
Mayo Clinic Laboratories, Mayo Clinic	RCV001449880	SCV001653277	pathogenic	not provided	2019-07-23	criteria provided, single submitter	clinical testing	An in-frame deletion involving exons 45-57 of the DMD gene.
Mayo Clinic Laboratories, Mayo Clinic	RCV001449881	SCV001653278	pathogenic	not provided	2019-06-06	criteria provided, single submitter	clinical testing	An out-of-frame deletion involving exon 45 of the DMD gene.
Neurogenetics Research Program, University of Adelaide	RCV001796573	SCV001737583	pathogenic	Cerebral palsy	2021-06-10	criteria provided, single submitter	research	Clinical diagnosis neurofibromatosis type 1. Cardiovascular complications are a feature of NF1.
Neurogenetics Research Program, University of Adelaide	RCV001796575	SCV001737585	pathogenic	Cerebral palsy	2021-06-10	criteria provided, single submitter	research
Kosik Lab, Neuroscience Research Institute, University of California Santa Barbara	RCV001810749	SCV001751549	pathogenic	Alzheimer disease	2021-07-01	criteria provided, single submitter	case-control
Molecular Pathology Research Laboratory, SA Pathology	RCV001541921	SCV001760553	pathogenic	Deafness-lymphedema-leukemia syndrome; GATA2 deficiency with susceptibility to MDS/AML	2021-07-06	criteria provided, single submitter	curation	PVS1, PS4_Supporting, PM2
Molecular Pathology Research Laboratory, SA Pathology	RCV001541922	SCV001760554	pathogenic	Deafness-lymphedema-leukemia syndrome; GATA2 deficiency with susceptibility to MDS/AML	2021-07-06	criteria provided, single submitter	curation	PVS1, PS4_Supporting, PM2
Molecular Pathology Research Laboratory, SA Pathology	RCV001541924	SCV001760556	pathogenic	Deafness-lymphedema-leukemia syndrome; GATA2 deficiency with susceptibility to MDS/AML	2021-07-06	criteria provided, single submitter	curation	PVS1, PS4_Supporting, PM2
Molecular Pathology Research Laboratory, SA Pathology	RCV001541925	SCV001760557	pathogenic	Deafness-lymphedema-leukemia syndrome; GATA2 deficiency with susceptibility to MDS/AML	2021-07-06	criteria provided, single submitter	curation	PVS1, PS4_Supporting, PM2
Molecular Pathology Research Laboratory, SA Pathology	RCV001541926	SCV001760558	pathogenic	Deafness-lymphedema-leukemia syndrome; GATA2 deficiency with susceptibility to MDS/AML	2021-07-06	criteria provided, single submitter	curation	PVS1, PS4_Supporting, PM2
Molecular Pathology Research Laboratory, SA Pathology	RCV001541927	SCV001760559	pathogenic	Deafness-lymphedema-leukemia syndrome; GATA2 deficiency with susceptibility to MDS/AML	2021-07-06	criteria provided, single submitter	curation	PVS1, PS4_Supporting, PM2
Molecular Pathology Research Laboratory, SA Pathology	RCV001541928	SCV001760560	pathogenic	Deafness-lymphedema-leukemia syndrome; GATA2 deficiency with susceptibility to MDS/AML	2021-07-06	criteria provided, single submitter	curation	PVS1, PS4_Supporting, PM2
New York Genome Center	RCV001542285	SCV001760968	uncertain significance	not provided	2020-07-10	criteria provided, single submitter	clinical testing	The inherited ~103 kb duplication identified overlaps with the well-known 1.4Mb recurrent 17q12 duplication [chr17:36,459,259-37,832,872, GRCh38, Reference 3]. The recurrent 1.4 Mb duplication contains 16 genes, four of which are located within the 103 kb duplication identified in this individual (ZNHIT3, MYO19, PIGW, and GGNBP2). Gene(s) responsible for clinical symptoms of the recurrent 1.4Mb 17q12 duplication are not identified yet [PMID: 26925472]. A 114 kb duplication involving full duplication of ZNHIT3, MYO19, and PIGW, as well as partial duplication of GGNBP2, TBC1D3G, and TBC1D3H is observed 117 times (55 homozygotes) in gnomAD SVs(v2.1). Given the uncertainty regarding the potential pathogenicity of ~103 kb duplication it is reported as a Variant of Uncertain Significance.
New York Genome Center	RCV001542324	SCV001761010	uncertain significance	Generalized epilepsy with febrile seizures plus, type 10	2020-07-03	criteria provided, single submitter	clinical testing	The inherited 5p12 duplication identified in this individual is a duplication on the short arm of chromosome 5, which contains the first 6 exons of the HCN1 gene. The distal breakpoint of this duplication is detected at Chr5:45270314, however due to the highly repetitive nature of centromeric regions, the proximal breakpoint cannot be determined by Whole Genome Sequencing, however microarray analysis suggests this duplication extends to the centromere of chromosome 5. The only gene contained in this region is HCN1, and the distal breakpoint confirms that exons 1-6 (NM_021072.4) of the HCN1 gene are contained within this duplication. This variant is absent from gnomAD(SV_v2.1) suggesting it is not a common benign variant in the populations represented in that database. This variant is absent from ClinVar, although a duplication containing exons 1-7 has been reported in ClinVar as a Variant of UncertainSignificance (VarID:646963). To our current knowledge neither this exact variant, nor similar intergenic duplications of HCN1, have been reported in affected individuals in the literature. Given the lack of compelling evidence for its pathogenicity and uncertainty regarding its functional consequence, the inherited 5p12 duplication containing exons 1-6 of the HCN1 gene is reported as a Variant of Uncertain Significance.
New York Genome Center	RCV001542388	SCV001761085	pathogenic	not provided	2020-07-17	criteria provided, single submitter	clinical testing	To our current knowledge, the exact duplication observed in this individual has not been previously reported in the literature, however the exact breakpoints of many 16q duplications reported in historical literature were not characterized by molecular methods and the exact breakpoints are uncertain. However, individuals with duplications similar to the one identified here (dup(16q11.2q21)) have been described with developmental delay, dysmorphic facial features, speech delay, intellectual disability, and additional variable features including recurrent infections, behavioral abnormalities, hyper-or hypotonia, and MRI abnormalities [PMID:21674840; PMID:22921637]. Additional individuals have been reported with proximal (16q11-q13) duplications contained within the larger duplication identified here with clinical phenotypes including developmental delay, variable intellectual disability or learning difficulties, variable dysmorphic features, speech delay, and behavioral abnormalities [PMID:16954678; PMID:10999840]. Given its presence de novo in this individual, absence in population databases, observation of several individuals with similar duplications in the literature, and its genomic content, the de novo 14.8MB duplication 16q11.2-q21 identified here is reported here as Pathogenic.
Otorhinolaryngology Lab - LIM32, University of Sao Paulo School of Medicine Clinics Hospital	RCV001729955	SCV001792241	pathogenic	Waardenburg syndrome type 2A		criteria provided, single submitter	research	de novo variant: proband with bilateral profound sensorineural hearing loss, hyperplasia of nasal root, One heterochromia iris and one hypoplastic blue iris, and hypochromic skin spots
GeneDx	RCV001584572	SCV001812480	likely benign	not provided	2019-10-21	criteria provided, single submitter	clinical testing
New York Genome Center	RCV001591740	SCV001815798	uncertain significance	not provided	2020-09-19	criteria provided, single submitter	clinical testing
GeneDx	RCV001649721	SCV001865196	benign	not provided	2019-08-21	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV001663741	SCV001879354	pathogenic	not provided	2022-04-27	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Multiple unrelated individuals with Duchenne muscular dystrophy (DMD) have been reported with similar deletions of exons 46-55. Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV001663743	SCV001879356	likely pathogenic	not provided	2020-11-05	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. This deletion spans the last 8 exons of the CCM2 gene. Due to limitations of this analysis, the exact size of this deletion and how far it extends beyond the CCM2 gene is uncertain. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org).
Athena Diagnostics	RCV001663744	SCV001879358	uncertain significance	not provided	2021-06-11	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV001663745	SCV001879359	pathogenic	not provided	2021-04-05	criteria provided, single submitter	clinical testing	This variant is expected to severely disrupt protein function. In-frame deletions such as this one are typically associated with Becker muscular dystrophy (BMD). Yet, similar deletions of exons 56-60 have been identified in at least two individuals with Duchenne muscular dystrophy (DMD; PMID: 25972034, 26081009). This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org).
Athena Diagnostics	RCV001663746	SCV001879360	pathogenic	not provided	2021-01-25	criteria provided, single submitter	clinical testing	This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)). Similar deletions of exon 45-55 have been reported primarily in patients with Becker muscular dystrophy (BMD), several cases with Duchenne muscular dystrophy (DMD; PMID: 28332368, 28181689, 25972034, 17854090), and at least two dilated cardiomyopathy cases (PMID: 18261911).
Athena Diagnostics	RCV001663747	SCV001879361	pathogenic	not provided	2023-06-30	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Multiple unrelated individuals with Duchenne muscular dystrophy (DMD) have been reported with similar deletions of exon 52. Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV001663748	SCV001879362	pathogenic	not provided	2022-06-29	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Multiple unrelated males with Duchenne muscular dystrophy (DMD) have been reported with similar deletions of exons 50-52. This variant has not been reported in large, multi-ethnic general populations. (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV001663749	SCV001879363	pathogenic	not provided	2022-04-08	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Multiple unrelated individuals with Duchenne muscular dystrophy (DMD) have been reported with similar deletions of exons 49-52. Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV001663750	SCV001879364	pathogenic	not provided	2022-04-27	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Multiple unrelated individuals with Duchenne muscular dystrophy (DMD) have been reported with similar deletions of exons 48-52. This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV001663751	SCV001879365	pathogenic	not provided	2022-03-23	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. A similar deletion of exons 46-51 has been identified in at least one individual with Duchenne muscular dystrophy (DMD). Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV001663752	SCV001879366	pathogenic	not provided	2020-10-30	criteria provided, single submitter	clinical testing	This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In-frame deletions such as this one are typically associated with Becker muscular dystrophy (BMD). Yet, deletions of exons 45-51 have been reported in patients with BMD and Duchenne muscular dystrophy (DMD).
Athena Diagnostics	RCV001663753	SCV001879367	pathogenic	not provided	2023-05-19	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Similar deletions of exons 45-50 have been reported in multiple unrelated individuals with DMD. At least one BMD case has also been reported (PMID: 28116794). Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV001663755	SCV001879369	likely pathogenic	not provided	2021-02-26	criteria provided, single submitter	clinical testing	This variant is presumed to be inserted in tandem within the DMD gene and would maintain the transcript's reading frame, but is expected to disrupt protein function. Similar duplications of exons 45-49 have been identified in at least one male with Becker muscular dystrophy (BMD, PMID: 33101180), as well as multiple males with Duchenne muscular dystrophy (DMD, PMID: 28610567, 25751470, 17259292, 9800909). This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org).
Athena Diagnostics	RCV001663756	SCV001879370	pathogenic	not provided	2022-10-20	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Multiple unrelated individuals with Duchenne muscular dystrophy (DMD) have been reported with similar deletions of exons 46-48. This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV001663757	SCV001879371	pathogenic	not provided	2022-05-10	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Similar deletions of exons 46-47 have been reported primarily in patients with Duchenne muscular dystrophy (DMD), and also in a few individuals with Becker muscular dystrophy (BMD). Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV001663758	SCV001879372	pathogenic	not provided	2020-10-22	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Similar deletions of exon 45 have been reported primarily in patients with Duchenne muscular dystrophy (DMD), and also in a few individuals with Becker muscular dystrophy (BMD; PMID: 19937601).
Athena Diagnostics	RCV001663759	SCV001879373	pathogenic	not provided	2022-10-04	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. A similar deletion of exon 44 has been identified in multiple unrelated individuals presenting with Duchenne muscular dystrophy (DMD). Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV001663760	SCV001879374	likely pathogenic	not provided	2021-05-11	criteria provided, single submitter	clinical testing	This variant is likely to be inserted in tandem within the DMD gene and would maintain the transcript's reading frame, but is expected to disrupt protein function. A similar duplication of exons 3-15 has been identified in at least one male with a dystrophinopathy. Similar variants have not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org).
Athena Diagnostics	RCV001663761	SCV001879375	likely pathogenic	not provided	2020-11-16	criteria provided, single submitter	clinical testing	This variant is presumed to be inserted within the DMD gene, thus expected to result in the loss of a functional protein. A similar duplication of exons 5-7 has been identified in at least one individual with Duchenne muscular dystrophy (DMD). This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org).
Athena Diagnostics	RCV001663762	SCV001879376	pathogenic	not provided	2020-10-27	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Out-of-frame deletions such as this one are typically associated with Duchenne muscular dystrophy (DMD). Yet, deletions of exons 3-7 have been reported in patients with DMD, Becker muscular dystrophy (BMD), and intermediate dystrophinopathies.
Athena Diagnostics	RCV001663763	SCV001879377	pathogenic	not provided	2021-01-12	criteria provided, single submitter	clinical testing	This deletion spans the entire coding sequence of the SPAST gene and is expected to result in the loss of a functional protein. Due to limitations of this analysis, the exact size of this deletion event is unknown. The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). A similar variant has been identified in at least one individual with clinical features associated with this gene.
Athena Diagnostics	RCV001663764	SCV001879378	pathogenic	not provided	2022-07-26	criteria provided, single submitter	clinical testing	Similar deletions of exons 8-17 have been identified in multiple individuals with clinical features associated with this gene. Similar variants have not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). The variant is located in a region that is considered important for protein function and/or structure.
Athena Diagnostics	RCV001663766	SCV001879381	pathogenic	not provided	2021-02-09	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Similar variants have not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). A similar deletion of exon 10 has been identified in at least one individual with clinical features associated with this gene.
New York Genome Center	RCV001784115	SCV002025630	uncertain significance	not provided	2020-06-11	criteria provided, single submitter	clinical testing
New York Genome Center	RCV001784120	SCV002025638	uncertain significance	not provided	2020-04-25	criteria provided, single submitter	clinical testing
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV001801231	SCV002047443	pathogenic	Developmental and epileptic encephalopathy, 9		criteria provided, single submitter	research
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV001807689	SCV002055985	pathogenic	Thrombocytopenia 5		criteria provided, single submitter	research
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV001807691	SCV002055987	pathogenic	Hereditary von Willebrand disease		criteria provided, single submitter	research
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV001807693	SCV002055989	pathogenic	Hereditary factor XI deficiency disease		criteria provided, single submitter	research
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV001807694	SCV002055990	uncertain significance	Hereditary factor XI deficiency disease		criteria provided, single submitter	research
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV001807695	SCV002055991	likely pathogenic	Factor X deficiency; Factor VII deficiency		criteria provided, single submitter	research
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV001807696	SCV002055992	uncertain significance	Hereditary factor IX deficiency disease		criteria provided, single submitter	research
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV001807697	SCV002055993	pathogenic	Bleeding disorder, platelet-type, 21		criteria provided, single submitter	research
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV001807700	SCV002055996	pathogenic	Hereditary thrombocytopenia and hematological cancer predisposition syndrome associated with RUNX1		criteria provided, single submitter	research
New York Genome Center	RCV001839062	SCV002098953	pathogenic	Syndromic X-linked intellectual disability Lubs type	2021-02-19	criteria provided, single submitter	clinical testing	The Xq27.1-q28 duplication is an approximately 13.8MB gain on the long arm of the X chromosome. While the centromeric breakpoint was identified with whole genome sequencing, the telomeric breakpoint of this duplication is within a low copy repeat (LCR) region and is poorly mapped with genome sequencing technology. Microarray analysis suggests the telomeric breakpoint occurs between the L1 and L2 region at the Int22h1 border (see [PMID:29341460]) with the telomeric breakpoint between genes CTAG1B and FAM223B. Of note, this duplication does NOT contain the critical region associated with Int22h1/Int22h2 mediated Xq28 duplication syndrome [PMID:26962617]. While partial duplications of Xq28 are not common, a similar copy number gain to the one identified here, not including the distal end of the X chromosome has been reported in ClinVar as Pathogenic [VarID:58691]. The duplication observed here contains over 200 genes, approximately 111 of which are OMIM associated, and includes disease associated genes GDI1[MIM#300104], FLNA[MIM#300017], FMR1[MIM#309550], NSDHL[MIM#300275], FAM58A [MIM#300708], NAA10[MIM#300013], and MECP2[MIM#300005]. Of these, duplications of MECP2 are associated with a well-known MECP2/Xq28 duplication syndrome, characterized in males by developmental delay, intellectual disability, gastrointestinal disturbances, spasticity, seizures, and additional variable clinical manifestations [PMID:22679399]. It has been suggested that the size of the Xq28 duplication including MECP2 is correlated with the degree of severity, and that larger duplications including RAB39B, which is NOT contained within the duplication identified here, are more clinically severe than smaller duplications not extending to this region [PMID:30788845]. Females with MECP2/Xq28 duplication syndrome often have extreme or complete skewing of X-chromosome inactivation and have mild phenotypes or are asymptomatic [PMID: 22679399], however affected females as well as inter-and intra-familial variability have been observed [PMID:29141583, 28257338, 27761913, 27247049, others]. This variant was identified as a de novo variant in an individual submitted for clinical testing. The Xq27.1-q28 duplication identified in this individual is reported here as Pathogenic.
Rare Disease Group, University of Exeter	RCV002281191	SCV002102567	likely pathogenic	SLC4A10-related neurodevelopmental disorder	2022-01-22	criteria provided, single submitter	research
Laboratory of Inherited Metabolic Diseases, Research centre for medical genetics	RCV001843999	SCV002103299	likely pathogenic	Mucopolysaccharidosis type 6		criteria provided, single submitter	research	The ARSB mRNA analysis demonstrated the premature transcription termination after the exon 4. Identified in-trans with the c.966G>A (p.Trp322Ter) pathogenic variant.
Laboratorio de Citogenómica y Microarreglos, Universidad Autonoma de Nuevo Leon	RCV002273839	SCV002106412	likely pathogenic	Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome	2022-03-22	criteria provided, single submitter	research	The present case involved breakpoint junctions and deletion between SH3 (that is, downstream DH1) and DH2 domains and DH2 and PH2 domains, that is, partially deleting GEF2D, a domain that activates RHOA. Although it does not affect DH1, this intragenic deletion included DH2 and could have resulted in aberrant shortened mRNAs and proteins, which, in turn, undergo rapid decay and consequently hypoactivation of RHOA. Because truncating variants (including those in DH2) resulting in a shortened protein and haploinsufficiency have an effect like those affecting GEF1D, the present disruption of TRIO most likely caused the patient’s MRD44-like phenotype, including mild ID, microcephaly, and facial features (Pengelly 2016, Ba 2016, Schultz-Rogers, 2020).
Laboratory of Inherited Metabolic Diseases, Research centre for medical genetics	RCV001849900	SCV002107169	likely pathogenic	Mucopolysaccharidosis, MPS-IV-B		criteria provided, single submitter	research	The GLB1 mRNA analysis demonstrated the inclusion of the 18 b.p. fragment of the intron 5 (NC_000003.11:g.33100082_33100099) r.552_553insCATTTCTACCATGGGAAG. Detected in-trans with the pathogenic c.808T>G (p.Tyr270Asp) variant.
Provincial Medical Genetics Program of British Columbia, University of British Columbia	RCV002067565	SCV002320830	pathogenic	Multiple acyl-CoA dehydrogenase deficiency	2022-01-01	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002227583	SCV002506618	uncertain significance	Becker muscular dystrophy; Duchenne muscular dystrophy	2021-05-14	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002227585	SCV002506620	likely pathogenic	Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome	2021-05-21	criteria provided, single submitter	clinical testing	The chr5:g.141572725_141615700del variant is a homozygous copy loss of coding exons 2-16 (total 28) as well as the 5’ and 3’ flanking intronic sequences and is present in one of the larger regions of homozygosity, as seen in the microarray data. The deleted exons (except one exon) are present in all the Refseq transcripts of DIAPH1. The variant is absent from gnomAD and DGV, suggesting it is not a common benign variant in the populations represented in these databases. This variant is not present in ClinVar, and to our current knowledge has not been identified in any affected individuals in the literature, however, other bi-allelic loss of function variants in DIAPH1 have been described in affected individuals with seizures, cortical blindness, microcephaly syndrome [MIM 616632; 2,3]. Given the predicted deleterious nature of this homozygous multi-exon deletion and its absence in population databases, the chr5:g.141572725_141615700del identified is reported as Likely Pathogenic.
New York Genome Center	RCV002227597	SCV002506634	uncertain significance	not provided	2021-06-30	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002247703	SCV002506671	pathogenic	Chromosome 3q29 microdeletion syndrome	2021-05-14	criteria provided, single submitter	clinical testing	The de novo deletion overlaps with 3q29 recurrent microdeletion region (includes DLG1), which has been curated by ClinGen to have “sufficient evidence to supportthe haploinsufficiency” [https://dosage.clinicalgenome.org/clingen_region.cgi?id=ISCA-37443]. Genes responsible for 3q29 deletion syndrome have not been definitively defined yet however,DLG1, FBXO45, PAK2, and RNF168 have been implicated [PMIID:27656750] and are located within the 1.5Mb region deleted here. Based on the available evidence, the de novo heterozygous ~1.5Mb interstitial deletion identified here is reported as Pathogenic.
New York Genome Center	RCV002227664	SCV002506727	uncertain significance	not provided	2021-06-22	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002227667	SCV002506730	uncertain significance	not provided	2021-05-21	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002227670	SCV002506734	uncertain significance	not provided	2021-07-09	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002227708	SCV002506791	uncertain significance	not provided	2021-05-21	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002227715	SCV002506801	pathogenic	Distal 16p11.2 microdeletion syndrome	2021-07-16	criteria provided, single submitter	clinical testing	The minimal deleted region in this de novo 16p11.2 deletion contains 12 genes, 9 of which are protein-coding and are OMIM-annotated (ATXN2L, TUFM, SH2B1, ATP2A1, RABEP2, CD19, NFATC2IP, SPNS1, and LAT). Of these, 4 genes are disease-associated; TUFM (autosomal recessive Combined oxidative phosphorylation deficiency 4; MIM#610678), ATP2A1 (autosomal recessive Brody Myopathy; MIM#617514), CD19 (autosomal recessive Immunodeficiency, common variable, 3, MIM# 613493), and LAT (autosomal recessive Immunodeficiency 52, MIM# 617514). Chromosome 16p contains several low copy repeat sequences, called BP1-BP5, and non- homologous recombination between these sequences leads to syndromes associated with recurrent copy number gains and losses. The ~220 Kb deletion observed here is between recurrent breakpoint regions BP2 and BP3 located in the distal region of 16p11.2. The minimal deleted region completely overlaps with 16p11.2 recurrent region (distal, BP2-BP3) (includes SH2B1), which has been curated by ClinGen to have “sufficient evidence for dosage pathogenicity” [https://dosage.clinicalgenome.org/clingen_region.cgi?id=ISCA-37486]. Based on the available evidence, the de novo heterozygous ~220 Kb interstitial 16p11.2 deletion is reported as Pathogenic.
New York Genome Center	RCV002227717	SCV002506810	pathogenic	Chromosome 1q21.1 duplication syndrome	2021-06-01	criteria provided, single submitter	clinical testing	The ~1.38Mb duplication on the long arm of chromosome 1 (1q21.1) is a recurrent microduplication that contains 42 genes, 9 of which are OMIM associated. Based on the available evidence, e.g., absence in population databases, observation of several individuals with similar duplications in the literature, and its genomic content, the inherited ~1.38Mb duplication in the 1q21.1 region is reported as Pathogenic.
New York Genome Center	RCV002227746	SCV002506849	uncertain significance	not provided	2021-06-25	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002227747	SCV002506850	uncertain significance	not provided	2021-06-25	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002227754	SCV002506859	uncertain significance	not provided	2021-06-25	criteria provided, single submitter	clinical testing	The exact duplication seen here is not reported before in the literature. However, a Microtriplication overlapping with this duplication has been reported in two unrelated patients whose clinical features include distinctive facial dysmorphisms, short stature with small extremities, keratoconus, overweight, and intellectual disability [PMID: 21617255]. Seizures were not reported in both patients [PMID: 21617255]. Based on the available evidence, the inherited ~1.26Mb duplication identified on 11q24.1 is reported as a variant of uncertain significance.
New York Genome Center	RCV002227763	SCV002506868	uncertain significance	Neurodevelopmental disorder	2021-07-02	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002227783	SCV002506892	uncertain significance	7p22.1 microduplication syndrome	2021-07-08	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002227787	SCV002506896	uncertain significance	not provided	2021-05-07	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002227822	SCV002506957	uncertain significance	Wilson-Turner syndrome	2021-06-04	criteria provided, single submitter	clinical testing	This exact ~444Kb interstitial duplication identified on Xq11.2-q12 is not reported in the literature to the best of our knowledge. A similar sized duplication has 0.0003162 allele frequency in the gnomAD SVs v2.1 database (Total allele number = 15,814. Individuals with heterozygous duplication = 2, individuals with hemizygousduplication = 3, individuals with homozygous duplication = none). Based on the available evidence, the inherited ~444Kb interstitial duplication identified on Xq11.2-q12 is reported as a variant of uncertain significance.
New York Genome Center	RCV002227826	SCV002506965	likely pathogenic	not provided	2021-04-30	criteria provided, single submitter	clinical testing	The deleted region contains ~54 genes, 35 of which are protein-coding. Among these, 26 genes are OMIM-annotated, 8 of which are disease-associated (HTT, DOK7, LRPAP1, ADRA2C, MSX1, EVC, EVC2, WFS1). Heterozygous pathogenic variants in MSX1 have been associated with autosomal dominant Ectodermal dysplasia 3, Witkop type [MIM#189500; AD], Orofacial cleft 5 [MIM#608874; AD], and Tooth agenesis, selective, 1, with or without orofacial cleft [MIM#106600; AD]. Pathogenic variants in EVC and EVC2 have been associated with autosomal dominant Weyers acrofacial dysostosis [MIM#193530, AD] as well as autosomal recessive Ellis-van Creveld syndrome [MIM#225500, AR]. Heterozygous pathogenic variants in WFS1 have been associated with autosomal dominant Cataract 41 [MIM#116400; AD], {Diabetes mellitus, noninsulin-dependent, association with} [MIM#125853;AD], Wolfram-like syndrome, autosomal dominant [MIM#614296; AD], and Deafness, autosomal dominant 6/14/38 [MIM#600965; AD]. Further, multiple genes in the deleted region (HTT, KIAA0232, JAKMIP1, CRMP1, TBC1D14, GRPEL1) are constrained for loss of function variants (gnomADv2 pLi >= 0.9). The deleted region was not commonly seen in the online normal human genetic variation database. The exact deletion seen in this individual has not been reported before in the literature, to our knowledge. However, larger distal deletions at 4p16.3 which extend to this region have been seen in Wolf-Hirschhorn syndrome(WHS) [PMID: 24357569]. The deletion observed in this individual does not overlap with the WHS critical region. Based on the gene content and the size of this deletion, it is reported here as Likely Pathogenic.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002247710	SCV002515974	pathogenic	Gastrointestinal stromal tumor; Paragangliomas 4; Pheochromocytoma	2021-10-06	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002247711	SCV002515975	likely pathogenic	Microcornea-myopic chorioretinal atrophy	2021-07-06	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002247713	SCV002515977	pathogenic	Pulmonary valve stenosis; Short stature; Failure to thrive; Scoliosis; Nystagmus; Microcephaly; Intellectual disability; Gray matter heterotopia; Parietal foramina; Proportionate short stature; Intellectual disability, severe	2021-04-14	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002247720	SCV002515982	pathogenic	Chromosome 2q37 deletion syndrome	2022-02-22	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002247722	SCV002515984	pathogenic	ZTTK syndrome	2021-03-19	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002247723	SCV002515985	pathogenic	Chromosome 1p36 deletion syndrome	2021-03-19	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002247726	SCV002515987	pathogenic	Velocardiofacial syndrome	2021-10-04	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002247731	SCV002515992	pathogenic	Autoinflammatory syndrome, familial, Behcet-like	2021-10-14	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002247737	SCV002515998	pathogenic	Chromosome 9p deletion syndrome	2022-02-10	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002247738	SCV002515999	likely pathogenic	Chorea-acanthocytosis	2021-08-18	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002247741	SCV002516002	pathogenic	Suleiman-El-Hattab syndrome	2022-01-31	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002247742	SCV002516003	pathogenic	Immunodeficiency 33; Ectodermal dysplasia and immunodeficiency 1; Incontinentia pigmenti syndrome; Immunodeficiency 47	2022-02-24	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002247743	SCV002516012	pathogenic	Splenomegaly; Decreased circulating antibody concentration	2022-02-24	criteria provided, single submitter	clinical testing
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV002247751	SCV002516015	likely pathogenic	Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies	2021-08-18	criteria provided, single submitter	clinical testing
Undiagnosed Diseases Network, NIH	RCV002253059	SCV002523165	uncertain significance	ATAD3 gene cluster related condition	2020-07-02	criteria provided, single submitter	clinical testing
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital	RCV002254460	SCV002525642	pathogenic	not provided	2021-01-29	criteria provided, single submitter	clinical testing	Exon-level microarray analysis identified an approximately 365 Kb deletion in 16q24.1 including the FOXF1 gene and its upstream regulatory region, including the non-coding RNA genes LINC01081 and LINC01082. Due to the nature of this array platform, with probes concentrated within exons, the actual deletion may extend into flanking intergenic regions, but it does not appear to include the neighboring FOXC2 gene.
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002264893	SCV002546516	pathogenic	Gollop-Wolfgang complex	2022-06-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002264898	SCV002546523	pathogenic	Split hand-foot malformation 5	2022-06-07	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002264899	SCV002546524	pathogenic	Chromosome 17P13.3, telomeric, duplication syndrome	2022-06-07	criteria provided, single submitter	research
New York Genome Center	RCV002266567	SCV002548571	uncertain significance	not provided	2021-07-30	criteria provided, single submitter	clinical testing	Duplications and deletions involving CNTN6 gene have been implicated as possible susceptibility factors for neurodevelopmental disorders including developmentaldelays, intellectual disability, autism spectrum disorder, and seizures [PMID: 26257835, 30508811]. There are a considerable number of individuals with duplicationsand deletions spanning this CNTN6 region in both Database of Genome Variants (DGV) and gnomAD, which indicates a potential tolerance of genomic imbalance inthis region. Further, the ClinGen dosage sensitivity curation for CNTN6 duplications found no evidence for dosage pathogenicity (Triplosensitivity score: 0). Inheritance from an unaffected parent has been reported for CNTN6 duplications indicating incomplete penetrance and/or phenotypic heterogeneity [PMID:26257835]. The clinical significance of CNTN6 partial duplications is currently uncertain [PMID: 30836150]. Given the lack of compelling evidence for its pathogenicity, the inherited ~580 Kb duplication seen in this individual is reported as a Variant of Uncertain Significance.
New York Genome Center	RCV002266588	SCV002548603	uncertain significance	7p22.1 microduplication syndrome	2021-08-06	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002266602	SCV002548623	uncertain significance	not provided	2021-05-21	criteria provided, single submitter	clinical testing	The inherited Chr20:62941782_63658260dup is an approximately 716.5KB duplication at 20q13.33. This duplication contains 32 genes, 18 of which are OMIM associated including the partial duplication of the RTEL1 gene. Of these OMIM associated genes, 4 are associated with disease phenotypes including SLC17A9 (Porokeratosis 8, disseminated superficial actinic type; AD, MIM#616063), CHRNA4(Epilepsy, nocturnal frontal lobe, 1; AD, MIM#600513), KCNQ2 (Developmental and epileptic encephalopathy 7; AD, MIM#613720, Myokymia; AD, MIM#121200,Seizures, benign neonatal, 1; AD, MIM#121200), and RTEL1 (Dyskeratosis congenita, autosomal dominant 4; AD,AR, MIM#615190, Dyskeratosis congenita, autosomalrecessive 5; AD, AR, MIM#615190; Pulmonary fibrosis and/or bone marrow failure, telomere-related, 3; AD, MIM#616373). This copy number variant is absent from population databases gnomAD(v2.1.1) and the Database of Genomic Variants (DGV). This variant is absent from ClinVar, and to our current knowledge this exact copy number gain has not been reported in affected individuals in the literature. While a similar reciprocal 20q13.33 deletion has been observed in individuals with developmental delays and seizures [PMID:25052858, 26030193, others], a duplication in this region similar to the one identified here has not been described to our current knowledge. Given the lack of compelling evidence for its pathogenicity, the inherited Chr20:62941782_63658260dup is reported as a Variant of Uncertain Significance.
New York Genome Center	RCV002266628	SCV002548664	uncertain significance	Luscan-Lumish syndrome	2021-07-16	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002266707	SCV002548780	likely pathogenic	Landau-Kleffner syndrome	2021-08-20	criteria provided, single submitter	clinical testing	This ~185Kb deletion contains the last 9 protein coding exons (6 through 14) as well as 3'Untranslated Region (3'UTR) of the GRIN2A gene. Approximately 75% of the GRIN2A protein is encoded by these exons (1,090 out of 1,464 amino acid resides; from p.Val375 through stop-codon). The variant is absent from the gnomAD SVs(v2.1) database suggesting it is not a common benign variant in the populations represented in that database. The exact same deletion has not been reported in affected individuals in the literature. However, several partial gene deletions affecting exons 6 to 14 of the GRIN2A gene have been reported in individuals affected with GRIN2A-related disorders [PMID: 30544257, 29655203]. Although the proband has inherited this deletion from his asymptomatic parent, given the wide spectrum of associated phenotypic severity, documented incomplete penetrance, and due to the expected loss-of-function effect of this variant, the inherited ~185Kb deletion is reported as Likely Pathogenic.
New York Genome Center	RCV002266743	SCV002548831	uncertain significance	not provided	2021-08-20	criteria provided, single submitter	clinical testing	The inherited Xp11.22 duplication observed here is absent from gnomAD SVs(v2.1.1) and the Database of Genomic Variants (DGV) suggesting it is not a common benign variant in the populations represented in that database. While this exact variant has not been reported in ClinVar, two copy number gains contained within the one identified here have been reported as both Likely Pathogenic (VarID:150778) and a Variant of Uncertain Significance (VarID:144464). Many larger duplications containing SHROOM4 have been reported in affected individuals in the literature, although these larger duplications contain many additional genes within the same copy number gain as SHROOM4 [PMID:26692240, 19716111, 25425167]. A small duplication containing the DGKK gene and exons 4-10 of the SHROOM4 gene was identified in a male with developmental delay, choanal atresia, ventricular septal defect, and camptodactyly [PMID:22659343]. However, full duplications of SHROOM4 have been identified in control individuals as well [PMID:26692240]. Given the uncertainty regarding the functional consequence of the inherited Xp11.22 duplication identified here, it is reported as a Variant of Uncertain Significance.
New York Genome Center	RCV002266744	SCV002548832	uncertain significance	not provided	2021-08-20	criteria provided, single submitter	clinical testing	The 21q21.1 mosaic deletion identified here is absent from gnomAD SVs(v2.1.1) and the Database of Genomic Variants (DGV) suggesting it is not a common benign variant in the populations represented in that database. While larger deletions and partially overlapping deletions have been reported in ClinVar, neither this exact deletion, nor a smaller deletion completely contained within it have been reported. This exact deletion has not been reported in the literature, although larger or partially overlapping deletions in this region were identified in individuals with variable phenotypes including developmental delay, intellectual disability, autism and seizures [PMID:25464110, 27625702]. Given the lack of compelling evidence for its pathogenicity, the 21q21.1 mosaic deletion identified here is reported as a Variant of Uncertain Significance.
New York Genome Center	RCV002266756	SCV002548844	uncertain significance	not provided	2021-07-23	criteria provided, single submitter	clinical testing	The approximately 918KB duplication observed at 9p24.1 is absent from gnomAD SVs (v2.1) and the database of genomic variants (DGV), suggesting it is not a common benign variant in the populations represented in those databases. The exact duplication observed here has not been reported in available databases, however duplications contained within or partially overlapping the one identified here have been reported in individuals with neurodevelopmental disorders [PMID:23731025, 21841781], however in at least one case the duplication was found to be inherited from a presumably unaffected parent [PMID:23731025]. Given the lack of compelling evidence for its pathogenicity the 9p24.1 duplication identified here is reported as a Variant of Uncertain Significance.
New York Genome Center	RCV002266766	SCV002548861	pathogenic	not provided	2021-09-17	criteria provided, single submitter	clinical testing	The 3.81MB 16q12.2q21 deletion identified here has not been observed in the Database of Genomic Variants (DVG) nor in gnomAD SVs(v2.1) suggesting it is not a common benign variant in the populations represented in this database. This variant is not reported in ClinVar, and while the exact deletion identified here has not been reported in affected individuals in the literature, deletions with similar genomic content or fully contained within this deletion have been reported in three individuals [PMID: 32045705, 20803649]. The 3.81MB, 16q12.2q21 copy number loss identified here is reported as Pathogenic.
New York Genome Center	RCV002266770	SCV002548867	uncertain significance	not provided	2021-07-16	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002266809	SCV002548922	uncertain significance	not provided	2021-10-07	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002266854	SCV002548985	uncertain significance	not provided	2021-06-04	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002266887	SCV002549025	uncertain significance	not provided	2021-06-04	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV002271997	SCV002555543	uncertain significance	Duchenne muscular dystrophy	2021-04-30	criteria provided, single submitter	clinical testing	A paternally-inherited heterozygous deletion of exons 27-29 in DMD was identified by prenatal genetic counseling testing in 1 female proband with normal clinical findings (hg38: chrX:32,438,012-32,452,548). The variant is found in another individual in the proband’s family not affected with the expected phenotype. This intragenic variant is not predicted to cause a frameshift, and is more likely to escape nonsense mediated decay (NMD) and result in a truncated protein. The copy number loss in this gene has not been previously reported, but multi-exon deletions in DMD are usually associated with disease (ranging from mild Becker’s to severe Duchenne’s; and some female carriers can manifest with mild symptoms). A similar variant (in frame deletion of exons 28-29) was found in a male affected with Becker’s Muscular Dystrophy and two unaffected female siblings, from 1 family in the literature (PMID: 17259292). The location of the curated copy number loss is upstream of a known alternative splice site for the “B” isoform (Dp260) of DMD. This implies that the intronic ATG start site (in intron 29) is spared in this curated variant. In summary, while the clinical significance of the variant is uncertain, these data suggest that it is more likely to be benign. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1A: 0 points, 2E PVS1_moderate: 0.3 points, 3A: 0 points, 5C: -0.15 points, 5E: -0.30 points; Total: 0 points; Riggs 2020 (PMID: 31690835).
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002274294	SCV002558860	likely pathogenic	See cases	2022-08-02	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002274295	SCV002558861	likely pathogenic	See cases	2022-08-02	criteria provided, single submitter	research
Center for Reproductive Medicine and Prenatal Diagnosis, The First Hospital of Jilin University	RCV002274813	SCV002559239	pathogenic	Alstrom syndrome	2022-06-18	criteria provided, single submitter	clinical testing	Exon 1 of ALMS1 is located in the deletion range
New York Genome Center	RCV002276485	SCV002564247	uncertain significance	not provided	2021-09-26	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002275643	SCV002564305	uncertain significance	not provided	2021-09-03	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002275687	SCV002564377	pathogenic	Xq25 microduplication syndrome	2021-08-20	criteria provided, single submitter	clinical testing	This de novo 1.7MB Xq25 duplication is absent from gnomAD SVs (v2.1) and the Database of Genomic Variants (DGV) suggesting it is not acommon benign variant in the populations represented in those databases. While this exact duplication has not been reported in the literature, other similar duplications containing the GRIA3, XIAP, and STAG2 genes have been reported in several individuals with variable clinical features including intellectual disability,developmental delay, behavioral abnormalities and seizures [PMID:23637084, 24733578, 31609727]. Smaller duplications minimally including STAG2 have also been reported independently in individuals with a neurodevelopmental phenotype including developmental delay, intellectual disability, as well as autism spectrum disorder and epilepsy in a subset of individuals [PMID:25450604, 26443594, 25677961], suggesting STAG2 is a critical gene for the Xp25 duplication phenotype. Additionally, partial duplications of GRIA3 including the 5’ region through intron 5 [PMID:17568425] and exon 1-12 [PMID:19449417] have been reported in males with intellectual disability. While this exact duplication has not been reported in the literature, the presence of many affected individuals in the literature with smaller duplications contained within the one identified here, including microduplications of the STAG2 gene, results in the classification of the de novo 1.7MB Xq25duplication identified here as Pathogenic.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV002280352	SCV002568408	pathogenic	3p- syndrome	2022-08-25	criteria provided, single submitter	curation	A confirmed de novo heterozygous deletion ([GRCh38]13371737_20095506x1) in 3p25.1-p24.3 encompassing 82 genes was identified by whole exome sequencing of one individual with delayed speech and language development, global developmental delay, delayed gross motor development, delayed fine motor development, and delayed social development via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Neurodev Study (https://www.neurodevproject.org/).There is complete overlap with the KAT2B and SATB1 genes, which are not known to be haploinsufficient and have not been assessed by the ClinGen Dosage Sensitivity Working Group. Though dosage sensitivity has not been established, the Decipher database (https://www.deciphergenomics.org/) has predicted KAT2B and SATB1 genes to be haploinsufficient. Data from large population studies is insufficient to assess the frequency of this variant. A reported proband from the literature (PMID: 33513338) has a a copy-number loss in SATB1. This variant is confirmed de novo and the reported phenotype of the proband is nonspecific (intellectual disability, developmental delay, speech delay). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant chromosome 3pter-p25 deletion syndrome. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1A: 0 points, 2H: 0.15 points, 3C: 0.90 points, 4: 0.15 points, 5A: 0.15 points; Total: 1.35 points; Riggs 2020 (PMID: 31690835).
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV002280353	SCV002568409	pathogenic	Interstitial 6q microdeletion syndrome	2022-08-25	criteria provided, single submitter	curation	A confirmed de novo heterozygous deletion of 6q22.1q23.2 ([GRCh38] 115941808_133892653x1) encompassing 184 genes was identified by whole exome sequencing of one individual with intellectual development disorders and seizures via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Neurodev Study (https://www.neurodevproject.org/). There is complete overlap with the EYA4 gene, which is known to be haploinsufficient and has been assessed by the ClinGen Dosage Sensitivity Working Group. Additional genes, NUS1 and GJA1, also have evidence supporting haploinsufficiency, but have not yet been curated by the clingen dosage sensitivity group and do not meet the burden of evidence to support haploinsufficiency (PMID: 29100083; PMID: 11470490). Data from large population studies is insufficient to assess the frequency of this variant. In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant complex neurodevelopmental disorder. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1A: 0 points, 2A: 1.00 points, 3C: 0.90 points, 4: 0.0 points, 5A: 0.15 points; Total: 2.05 points; Riggs 2020 (PMID: 31690835).
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV002280354	SCV002568410	pathogenic	15q11q13 microduplication syndrome	2022-08-25	criteria provided, single submitter	curation	A confirmed de novo heterozygous triplication in 15q11.2-13.1 ([GRCh38]22810652-29822566x4) encompassing 171 genes was identified by whole exome sequencing of one individual with intellectual development disorders and seizures via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Neurodev Study (https://www.neurodevproject.org/). There is complete overlap with the 5q11.2q13 recurrent (PWS/AS) region (Class 2,BP2-BP3), which is known to be triplosenstive and has been assessed by the ClinGen Dosage Sensitivity Working Group. Data from large population studies is insufficient to assess the frequency of this variant. In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant Chromosome 15q11-q13 Duplication Syndrome. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1A: 0 points, 2A: 1.0 points, 3C: 0.90 points, 4: 0.0 points, 5A: 0.15 points; Total: 2.05 points; Riggs 2020 (PMID: 31690835).
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV002280355	SCV002568411	pathogenic	Chromosome 15q13.3 microdeletion syndrome	2022-08-25	criteria provided, single submitter	curation	A confirmed paternally inherited deletion in chromosome 15q13.2-13.3 ([GRCh38]30626003_32111997x1) encompassing 19 genes was identified by whole exome sequencing in one individual with autism, delayed speech and language development, global developmental delay, delayed gross motor development, expressive language delay, and delayed fine motor development via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Neurodev Study (https://www.neurodevproject.org/). Data from large population studies is insufficient to assess the frequency of this variant. There is nearly complete overlap with the 15q13.3 recurrent region (BP4-BP5) (includes CHRNA7), which is known to be haploinsufficient and has been assessed by the ClinGen Dosage Sensitivity Working Group. However, this region does show incomplete penetrance and there are case/control studies demonstrating enrichment in affected individuals (PMID: 25217958; PMID: 21844811). In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Chromosome 15q13.33 Deletion Syndrome. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1A: 0 points, 2B: 1.0 points, 3A: 0. points, 4: 0. points, 5: 0. points; Total: points; Riggs 2020 (PMID: 31690835).
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV002280356	SCV002568412	pathogenic	Chromosome 16p11.2 duplication syndrome	2022-08-25	criteria provided, single submitter	curation	A confirmed de novo heterozygous deletion of 16p11.2 ([GRCh38] 29663598_30188229x1) encompassing 30 genes was identified by whole exome sequencing of one individual with autism, delayed speech and language development, global developmental delay and abnormal social behavior via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Neurodev Study (https://www.neurodevproject.org/). There is complete overlap with the PRRT2 gene which is known to be haploinsufficient and has been assessed by the ClinGen Dosage Sensitivity Working Group. The additional gene, TAOK2, also has evidence supporting haploinsufficiency, but has not yet been curated by the clingen dosage sensitivity group (PMID: 29467497). Data from large population studies is insufficient to assess the frequency of this variant. In summary, this variant meets criteria to be classified as pathogenic for Chromosome 16p11.2 Deletion Syndrome, 593-KB. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1A: 0 points, 2A: 1.00 points, 3C: 0.45 points, 4: 0.0 points, 5A: 0.15 points; Total: 1.60 points; Riggs 2020 (PMID: 31690835).
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV002280357	SCV002568413	pathogenic	Deletion of long arm of chromosome 18	2022-08-25	criteria provided, single submitter	curation	A confirmed de novo heterozygous deletion of 18q21.33-q23 ([GRCh38]61,490,305_80,247,612x1) encompassing 129 genes was identified by whole exome sequencing of one individual with global developmental delay, delayed speech and language development, dystonia, delayed gross and fine motor development, steppage gait, and abnormal social behavior via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Neurodev Study (https://www.neurodevproject.org/). Data from large population studies is insufficient to assess the frequency of this variant. At least three probands from the literature (Yu et al. 2022, PMID: 21977138, PMID: 34616427) have a copy-number loss in 18q22.2q23 similar in genomic content to the variant in our study. Of these probands, two have deletions that are confirmed de novo, and the reported phenotypes are nonspecific (mild intellectual disability, developmental delay, motor delay, lack of expressive and receptive language). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant Chromosome 18 Deletion Syndrome. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1A: 0 points, 2B: 0 points, 3C: 0.90 points, 4C: 0.40 points, 5A: 0.15 points; Total: 1.45 points; Riggs 2020 (PMID: 31690835).
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV003232577	SCV002568414	pathogenic	Chromosome 22q11.2 deletion syndrome, distal	2022-08-25	criteria provided, single submitter	curation	A confirmed de novo heterozygous deletion in chromosome 22q11.21 ([GRCh38]18985739_21081116x1) encompassing 88 genes was identified by whole exome sequencing in two unrelated individuals with intellectual disability, with one also presenting with delayed speech and language development and the other presenting with seizures and delayed ability to walk, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Neurodev Study (https://www.neurodevproject.org/). There is complete overlap with the DGCR8 gene, which is not known to be haploinsufficient and has not been assessed by the ClinGen Dosage Sensitivity Working Group. Though dosage sensitivity has not been established, the Decipher database (https://www.deciphergenomics.org/) has predicted the DGCR8 gene to be haploinsufficient. Data from large population studies is insufficient to assess the frequency of this variant. More than 10 reported probands from the literature (PMID: 24311469, PMID: 33482818) have a copy-number loss in chromosome 22q11.21 similar in genomic content to the variant in our study. All of these probands have deletions that are confirmed de novo and the reported phenotypes of the probands are nonspecific (mild developmental delay, epilepsy, language delay). In summary, this variant meets criteria to be classified as pathogenic for Chromosome 22q11.21 deletion syndrome. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1A: 0 points, 2H: 0.15 points, 3C: 0.90 points, 4C: 0.90 points, 5A: 0.30 points; Total: 2.10 points; Riggs 2020 (PMID: 31690835).
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV003232578	SCV002568415	pathogenic	Chromosome 22q11.2 microduplication syndrome	2022-08-25	criteria provided, single submitter	curation	A confirmed de novo heterozygous duplication ([GRCh38]18985739_21081116x3) in chromosome 22q11.21 encompassing 88 genes was identified by whole exome sequencing in one individual with global developmental delay, delayed speech and language development, and delayed social development via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Neurodev Study (https://www.neurodevproject.org/). Data from large population studies is insufficient to assess the frequency of this variant. Two reported probands from the literature (PMID: 17250668; PMID: 26719767) have copy-number gains in chromosome 22q11.21 similar in genomic content to the variant in our study. Of these probands, one has a duplication that is confirmed de novo and in both probands the reported phenotypes are nonspecific (delay in social and language development, autism, neuromotor delay). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant Chromosome 22q11.21 duplication Syndrome. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1A: 0 points, 2B: 0 points, 3C: 0.90 points, 4C: 0.25 points, 5A: 0.15 points; Total: 1.30 points; Riggs 2020 (PMID: 31690835).
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV002280361	SCV002568416	pathogenic	Chromosome 22q13 duplication syndrome	2022-08-25	criteria provided, single submitter	curation	A confirmed de novo heterozygous duplication in chromosome 22q13.33 ([GRCh38]49883237_50740457x3) encompassing 39 genes was identified by whole exome sequencing in one individual with delayed speech and language development, intellectual disability, expressive language delay, and delayed ability to walk via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Neurodev Study (https://www.neurodevproject.org/). Data from large population studies is insufficient to assess the frequency of this variant. At least three reported probands from the literature (PMID: 2784604; PMID: 24153177) and one proband from the DECIPHER database (Decipher ID: 396055) have a copy-number gain in chromosome 22q13.33 similar in genomic content to the variant in our study. Of these probands, one has a duplication that is confirmed de novo, and the reported phenotypes of all probands are nonspecific (autism, ADHD, seizures, bipolar disorder). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant Chromosome 22q13 duplication Syndrome. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1A: 0 points, 2H: 0 points, 3C: 0.45 points, 4C: 0.45 points, 5A: 0.15 points; Total: 1.05 points; Riggs 2020 (PMID: 31690835).
ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	RCV002280381	SCV002568449	likely pathogenic	Hereditary factor XI deficiency disease		criteria provided, single submitter	clinical testing
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002286364	SCV002576315	uncertain significance	not specified	2021-05-25	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002286365	SCV002576316	uncertain significance	not specified	2022-09-28	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002286366	SCV002576317	uncertain significance	not specified	2022-09-28	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002286367	SCV002576318	uncertain significance	not specified	2022-09-28	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002286369	SCV002576320	pathogenic	not specified	2022-09-28	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002286370	SCV002576321	uncertain significance	not specified	2022-09-28	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002286371	SCV002576322	uncertain significance	not specified	2022-09-28	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002286372	SCV002576323	uncertain significance	not specified	2022-09-28	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002286373	SCV002576324	uncertain significance	not specified	2022-09-28	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002286374	SCV002576325	likely pathogenic	not specified	2022-09-28	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002286375	SCV002576326	pathogenic	5q35 microduplication syndrome	2021-05-25	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002286376	SCV002576327	uncertain significance	not specified	2022-09-28	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002286377	SCV002576328	uncertain significance	not specified	2022-09-28	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002286378	SCV002576329	uncertain significance	not specified	2022-09-28	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002286379	SCV002576330	uncertain significance	not specified	2022-09-28	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002286380	SCV002576331	uncertain significance	not specified	2021-05-25	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002286381	SCV002576332	uncertain significance	not specified	2021-05-25	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002286382	SCV002576333	uncertain significance	not specified	2021-05-25	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002286383	SCV002576334	uncertain significance	not specified	2021-05-25	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002286384	SCV002576335	uncertain significance	not specified	2021-05-25	criteria provided, single submitter	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV002286385	SCV002576336	uncertain significance	not specified	2021-05-25	criteria provided, single submitter	research
Institute for Medical Genetics and Human Genetics, Charité - Universitätsmedizin Berlin	RCV002287860	SCV002578132	pathogenic	Severe combined immunodeficiency due to DCLRE1C deficiency	2022-09-27	criteria provided, single submitter	clinical testing
Shaanxi Institute for Pediatric Diseases, Xi'an Children's Hospital	RCV003223355	SCV002584967	pathogenic	Pearson syndrome		criteria provided, single submitter	research
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV002294568	SCV002587056	pathogenic	Muscular dystrophy, limb-girdle, autosomal recessive 23		criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV002294569	SCV002587057	pathogenic	Muscular dystrophy, limb-girdle, autosomal recessive 23		criteria provided, single submitter	clinical testing
Department of Molecular Diagnosis and Cancer Prevention, Saitama Cancer Center	RCV002308493	SCV002600098	pathogenic	Lynch syndrome 1	2022-11-08	criteria provided, single submitter	clinical testing	This sequence change causes a complete deletion of the PMS2 gene. This variant has been detected in patients under 20 years of age with PMS2-deficient glioblastoma and colorectal adenocarcinoma in IHC, along with another variant, PMS2 (NM_000535.7): c.241G>T (p.Glu81*, located in trans). The patient is considered constitutional mismatch repair deficiency (CMMRD).
Ambry Genetics	RCV002379639	SCV002672400	likely pathogenic	Hereditary cancer-predisposing syndrome	2018-09-13	criteria provided, single submitter	clinical testing	The c.7388_7389insALU likely pathogenic variant results from an Alu element insertion located in coding exon 49 of the ATM gene. Alu element insertions contribute to pathogenicity by either disrupting the coding sequence or inducing aberrant splicing (Belancio VP et al. Semin. Cancer Biol. 2010 Aug;20:200-10; Deininger P et al. Genome Biol. 2011 Dec;12:236). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
New York Genome Center	RCV002468504	SCV002764450	uncertain significance	Brugada syndrome 3; Long qt syndrome 8	2021-12-01	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002468505	SCV002764451	uncertain significance	Maturity-onset diabetes of the young type 8	2021-11-15	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002468511	SCV002764465	uncertain significance	Maturity-onset diabetes of the young type 8	2020-12-09	criteria provided, single submitter	clinical testing
New York Genome Center	RCV002468550	SCV002764594	uncertain significance	Maturity-onset diabetes of the young type 8	2021-04-28	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV002475193	SCV002771489	pathogenic	not provided	2020-07-21	criteria provided, single submitter	clinical testing	Duplication of the APP locus has been reported in multiple unrelated families and/or individuals with clinical features of Alzheimer's disease. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org).
Athena Diagnostics	RCV002475194	SCV002771490	uncertain significance	not provided	2022-03-07	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV002475195	SCV002771491	pathogenic	not provided	2021-06-18	criteria provided, single submitter	clinical testing	A similar deletion involving all of CAPN3 and a portion of a neighboring gene has been identified in two families with limb-girdle muscular dystrophy type 2A (LGMD2A; PMID: 24715573). The frequency of similar variants in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org).
Athena Diagnostics	RCV002475196	SCV002771492	uncertain significance	not provided	2021-10-20	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV002475197	SCV002771493	pathogenic	not provided	2022-06-07	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Similar variants have not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual tested at Athena Diagnostics with clinical features associated with this gene.
Athena Diagnostics	RCV002475198	SCV002771494	pathogenic	not provided	2022-04-18	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Similar variants have been identified in multiple unrelated individuals with Duchenne muscular dystrophy (DMD). Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV002475199	SCV002771495	pathogenic	not provided	2023-06-13	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Similar deletions of exons 49-50 have been reported primarily in patients with Duchenne muscular dystrophy (DMD), and also in a few individuals with Becker muscular dystrophy (BMD; PMID: 19937601, 28610567). Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV002475200	SCV002771496	pathogenic	not provided	2022-03-01	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Similar deletions of exons 46-50 are reported primarily in patients with Duchenne muscular dystrophy (DMD), and also in a few rare cases with Becker muscular dystrophy (BMD; PMID: 16936400, 17253928). Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV002475201	SCV002771497	pathogenic	not provided	2022-06-28	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Multiple unrelated individuals with Duchenne muscular dystrophy (DMD) have been reported with similar deletions of exons 48-50. Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV002475202	SCV002771498	likely pathogenic	not provided	2021-07-26	criteria provided, single submitter	clinical testing	This variant is likely to be inserted in tandem within the DMD gene and is expected to disrupt protein function. Similar variants have not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). A similar duplication of exon 20 has been identified in at least one individual with Duchenne muscular dystrophy (DMD).
Athena Diagnostics	RCV002475203	SCV002771499	pathogenic	not provided	2023-08-24	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Similar deletions of exon 50 have been reported in multiple patients with DMD, and also a few cases with BMD (PMID: 28610567, 16834926). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV002475204	SCV002771500	pathogenic	not provided	2022-04-20	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Multiple unrelated males with Duchenne muscular dystrophy (DMD) have been reported with similar deletions of exons 8-11. Similar variants have not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org).
Athena Diagnostics	RCV002475205	SCV002771501	pathogenic	not provided	2021-07-30	criteria provided, single submitter	clinical testing	This variant is likely to be inserted in tandem within the DMD gene and would maintain the transcript's reading frame, but is expected to disrupt protein function. Similar duplications of exons 3-4 have been reported in multiple unrelated patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and intermediate dystrophinopathies. Similar variants have not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org).
Athena Diagnostics	RCV002475206	SCV002771502	pathogenic	not provided	2021-06-11	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)). Similar deletions of exons 42-43 have been reported in patients with Becker muscular dystrophy (BMD), Duchenne muscular dystrophy (DMD), and an intermediate dystrophinopathy (IMD).
Athena Diagnostics	RCV002475207	SCV002771503	pathogenic	not provided	2021-09-08	criteria provided, single submitter	clinical testing	Similar deletions of exons 3-4 have been reported in multiple individuals described as having BMD, and also in several with Duchenne muscular dystrophy (DMD; PMID: 1864612, 9048922, 12324874, 16049303), as well as in individuals where the type of dystrophinopathy was not specified. Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV002475208	SCV002771504	pathogenic	not provided	2021-06-15	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Similar variants have not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Similar deletions of exon 63 have been identified in individuals with Duchenne muscular dystrophy (DMD).
Athena Diagnostics	RCV002475209	SCV002771505	pathogenic	not provided	2022-06-10	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Multiple unrelated individuals with Duchenne muscular dystrophy (DMD) have been reported with similar deletions of exons 46-53. Similar deletions have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV002475210	SCV002771506	likely pathogenic	not provided	2021-08-25	criteria provided, single submitter	clinical testing	This variant is likely to be inserted in tandem within the DMD gene and would maintain the transcript's reading frame, but is expected to disrupt protein function. Similar duplication of exons 45-55 has been identified in at least one male with dystrophinopathy. Similar deletions have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV002475211	SCV002771507	pathogenic	not provided	2021-06-14	criteria provided, single submitter	clinical testing	This variant is likely to be inserted in tandem within the DMD gene and is expected to disrupt protein function. Similar variants have not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Similar duplications of exons 45-51 have been identified in multiple unrelated males with dystrophinopathies, including at least three with Duchenne muscular dystrophy (DMD; PMID: 15643612, 25482253, 28332368).
Athena Diagnostics	RCV002475212	SCV002771508	pathogenic	not provided	2022-08-18	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Multiple unrelated individuals with DMD have been reported with similar deletions of exon 18-44. Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV002475213	SCV002771509	pathogenic	not provided	2021-12-17	criteria provided, single submitter	clinical testing	Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)). Multiple unrelated individuals with Duchenne muscular dystrophy (DMD) have been reported with similar deletions of exons 8-13.
Athena Diagnostics	RCV002475214	SCV002771510	pathogenic	not provided	2016-11-04	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV002475215	SCV002771511	pathogenic	not provided	2022-04-07	criteria provided, single submitter	clinical testing	This deletion variant is predicted to maintain the open reading frame. However, due to the altered protein length, it is expected to severely disrupt protein function. Similar deletions of exons 49-51 have been reported in the literature to be associated with both Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and dilated cardiomyopathy (DCM). Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV002475216	SCV002771512	uncertain significance	not provided	2021-08-05	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV002475217	SCV002771513	pathogenic	not provided	2022-06-29	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Similar deletions of exons 46-49 have been reported primarily in patients with Duchenne muscular dystrophy (DMD), and also in a few individuals with Becker muscular dystrophy (BMD; PMID: 17259292, 34602496). Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV002475218	SCV002771514	pathogenic	not provided	2021-06-15	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). A similar deletion of exon 67 has been reported in at least one individual with Duchenne muscular dystrophy (DMD).
Athena Diagnostics	RCV002475219	SCV002771515	pathogenic	not provided	2022-03-15	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Similar deletions of exons 51-52 have been reported in multiple individuals described as having Duchenne muscular dystrophy (DMD), or in individuals where the type of dystrophinopathy was not specified. Similar variants have not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org).
Athena Diagnostics	RCV002475220	SCV002771516	likely pathogenic	not provided	2021-08-20	criteria provided, single submitter	clinical testing	This variant is expected to severely disrupt protein function. Similar variants have not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org).
Athena Diagnostics	RCV002475221	SCV002771517	likely pathogenic	not provided	2021-09-24	criteria provided, single submitter	clinical testing	This deletion variant is predicted to maintain the open reading frame. However, due to the altered protein length, this is predicted to result in abnormal protein function. Similar variants have not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Deletion of exons 49-55 has not been reported in the literature. Other in-frame deletions in this region (e.g. exons 49-53) have been reported in multiple patients with dystrophinopathy-related diseases.
Athena Diagnostics	RCV002475222	SCV002771518	likely pathogenic	not provided	2022-03-08	criteria provided, single submitter	clinical testing	This variant is likely inserted in tandem within the DMD gene (PMID: 25640679) and, if so, would severely disrupt protein function. A similar duplication of exons 53-60 has been reported in at least one male with Duchenne muscular dystrophy (DMD). Similar variants have not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org).
Athena Diagnostics	RCV002475223	SCV002771519	pathogenic	not provided	2022-02-28	criteria provided, single submitter	clinical testing	Similar deletions of exons 10-29 have been reported in multiple males described as having Becker muscular dystrophy (BMD), or in males where the type of dystrophinopathy was not specified. Similar variants have not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org).
Athena Diagnostics	RCV002475224	SCV002771520	pathogenic	not provided	2022-08-03	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Similar deletions of exons 35-50 have been reported in at least two individuals with DMD, and at least one with BMD. Similar variants have not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org).
Athena Diagnostics	RCV002475225	SCV002771521	pathogenic	not provided	2022-09-13	criteria provided, single submitter	clinical testing	This deletion is predicted to maintain the transcript reading frame, however, it also disrupts an important binding domain of the protein and is thus expected to severely disrupt function. Similar deletions of exon 3-44 have been reported in patients with DMD and those with BMD.
Athena Diagnostics	RCV002475226	SCV002771522	pathogenic	not provided	2022-02-15	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Similar variants have not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). A similar variant has been identified in at least one individual with clinical features associated with this gene.
Athena Diagnostics	RCV002475227	SCV002771523	pathogenic	not provided	2022-05-03	criteria provided, single submitter	clinical testing	This variant is expected to severely impact normal RNA splicing, and consequently, protein structure and/or function. Similar variants have been identified in multiple unrelated individuals with clinical features associated with this gene. Similar variants have not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org).
Athena Diagnostics	RCV002475228	SCV002771524	likely pathogenic	not provided	2021-08-25	criteria provided, single submitter	clinical testing	This deletion variant maintains the transcript's reading frame, but is expected to disrupt protein function. Similar variants have not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). A similar deletion of exons 14-16 has been identified in at least one individual with clinical features associated with this gene.
Athena Diagnostics	RCV002475229	SCV002771525	pathogenic	not provided	2021-08-26	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Similar variants have not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). A similar variant has been identified in at least one individual with clinical features associated with this gene.
Athena Diagnostics	RCV002475230	SCV002771526	pathogenic	not provided	2021-11-09	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. A similar variant has been identified in at least one individual with clinical features associated with this gene. Similar variants have not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org).
Athena Diagnostics	RCV002475231	SCV002771527	likely pathogenic	not provided	2022-01-05	criteria provided, single submitter	clinical testing	This deletion variant maintains the transcript's reading frame, but is likely to disrupt protein structure or function. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual tested at Athena Diagnostics with clinical features associated with this gene.
Laboratory of Medical Genetics, University of Torino	RCV002481168	SCV002774884	likely pathogenic	Developmental and epileptic encephalopathy, 54	2022-12-23	criteria provided, single submitter	clinical testing
Laboratory of Medical Genetics, University of Torino	RCV002481171	SCV002774889	likely pathogenic	Developmental and epileptic encephalopathy, 54	2022-12-23	criteria provided, single submitter	clinical testing
Laboratory of Medical Genetics, University of Torino	RCV002481172	SCV002774890	likely pathogenic	Developmental and epileptic encephalopathy, 54	2022-12-23	criteria provided, single submitter	clinical testing
Genomic Medicine, Universita Cattolica del Sacro Cuore	RCV002510483	SCV002817425	pathogenic	See cases	2022-12-21	criteria provided, single submitter	clinical testing	The variant is de novo.
Optical Genome Mapping Laboratory, Clinical Institute of Genomic Medicine, University Medical Center Ljubljana	RCV002510242	SCV002818293	uncertain significance	Pelizaeus-Merzbacher disease	2023-01-06	criteria provided, single submitter	clinical testing	This duplication initially identified by arrayCGH, containing the PLP 1 gene, and found in a male child was initially interpreted as pathogenic 1A, 2A. Optical genome mapping identified the part of the duplication containing the complete PLP1 gene to be inverted and the exact location of the invdup to be between two lamina-associated domains (LADs). Additionally, segregation of the extended family identified additional carriers, including an adult male without clinical manifestation of PLP1. On the basis of this evidence the variant was reclassified as a variant of uncertain significance (1A, 2A, 4J, total points: 0.70).
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV003154619	SCV003843209	likely pathogenic	See cases	2021-03-08	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV003154620	SCV003843213	likely pathogenic	Rubinstein-Taybi syndrome due to CREBBP mutations	2021-03-09	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV003154621	SCV003843214	pathogenic	See cases	2020-01-29	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV003154622	SCV003843215	pathogenic	See cases	2020-01-06	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV003154623	SCV003843216	likely pathogenic	See cases	2021-02-12	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV003154628	SCV003843234	pathogenic	See cases	2019-09-23	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV003154629	SCV003843235	uncertain significance	See cases	2021-11-17	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV003154631	SCV003843239	likely benign	See cases	2021-10-20	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV003154634	SCV003843243	pathogenic	See cases	2021-12-13	criteria provided, single submitter	clinical testing
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV003156207	SCV003845199	pathogenic	Peeling skin syndrome 1		criteria provided, single submitter	clinical testing
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV003156208	SCV003845201	pathogenic	Bartter disease type 3		criteria provided, single submitter	clinical testing
New York Genome Center	RCV003221320	SCV003915654	likely pathogenic	16p13.11 recurrent microdeletion syndrome	2021-10-06	criteria provided, single submitter	clinical testing	The inherited ~1.5Mb interstitial 16p13.11 BP2-BP3 deletion contains 14 OMIM associated genes, and 4 of those are disease associated (MYH11, ABCC6, NDE1, and ABCC1). This region harbors a cluster of low copy repeats that lead to recurrent copy number changes, mainly three single copy intervals between segmental duplications (PMID: 21150890, 19786961). Interval I includes the genes RRN3 and PDXDC1; Interval II includes MYH11, NDE1, and ABCC6, and Interval III includes XYLT1. Deletions and duplications most commonly include the genes in interval II but may extend to include intervals I and III (PMID:21150890, 19786961). The presence of these repeats makes mapping the exact breakpoints with short-read sequencing and/or microarray difficult. Deletions in this region are associated with 16p13.11 BP2-BP3 recurrent deletion syndrome, which has a high degree of phenotypic variability and confers susceptibility to a variety of developmental disorders including developmental delay, microcephaly, epilepsy, short stature, facial dysmorphism, and behavioral problems (PMID: 18550696, 19843651, 24246141). Microdeletions appear de novo or are inherited from mildly affected or completely normal parents in an autosomal dominant manner, suggesting that the microdeletion has incomplete penetrance and variable expressivity (PMID: 17480035, 18550696, 19843651). ClinGen haploinsufficiency score is 3 for this region meaning sufficient evidence for dosage pathogenicity. Based on the available evidence the 16p13.11 BP2-BP3 deletion identified here is classified as likely pathogenic.
New York Genome Center	RCV003221321	SCV003915655	pathogenic	22q11.2 deletion syndrome	2021-10-01	criteria provided, single submitter	clinical testing	The ~3Mb proximal 22q11.21 recurrent (DGS/VCFS) region (proximal, A-D) deletion identified here contains 44 OMIM associated genes, and 14 of those are diseases associated (includes TBX1). ClinGen Haploinsufficiency score is 3 for this region meaning sufficient evidence for dosage pathogenicity. Based on the available evidence the 22q11.2 proximal (A-D) deletion identified here is classified as pathogenic.
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV003226030	SCV003922110	uncertain significance	Dihydropteridine reductase deficiency	2023-05-02	criteria provided, single submitter	curation	The homozygous c.119+12119G>A variant in QDPR was identified by our study in one individual with hyperphenylalaninemia, global developmental delay, hypertonia, macrocephaly, seizures, constipation, drooling, dysphagia, and absent DHPR activity (PMID: 32022462). The phenotype of this individual homozygous for this variant is highly specific for dihydropteridine reductase deficiency based on the absent DHPR activity observed (PMID: 33903016). The c.119+12119G>A variant in QDPR has not been previously reported in individuals with dihydropteridine reductase deficiency, but has been identified in 0.06% (3/5190) of East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs898384584). Although this variant has been seen in the general population in a heterozygous state, its frequency is not high enough to rule out a pathogenic role. The affected individual with this variant had an alternate molecular basis for the disease (dihydropteridine reductase deficiency) (PMID: 32022462, ClinVar Variation ID: 626310), suggesting that this variant may not be pathogenic. Computational prediction tools, including splice predictors, and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the c.*119+12119G>A variant is uncertain. ACMG/AMP Criteria applied: PM3_Supporting, PP4, BP4, BP5 (Richards 2015).
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV003226031	SCV003922111	uncertain significance	Dihydropteridine reductase deficiency	2023-05-02	criteria provided, single submitter	curation	The homozygous c.119+4759T>C variant in QDPR was identified by our study in one individual with hyperphenylalaninemia, global developmental delay, hypertonia, macrocephaly, seizures, constipation, drooling, dysphagia, and absent DHPR activity (PMID: 32022462). The phenotype of this individual homozygous for this variant is highly specific for dihydropteridine reductase deficiency based on the absent DHPR activity observed (PMID: 33903016). The c.119+4759T>C variant in QDPR has not been previously reported in individuals with dihydropteridine reductase deficiency, but has been identified in 0.02% (13/68032) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs1167539604). Although this variant has been seen in the general population in a heterozygous state, its frequency is not high enough to rule out a pathogenic role. The affected individual with this variant had an alternate molecular basis for the disease (dihydropteridine reductase deficiency) (PMID: 32022462, ClinVar Variation ID: 626310), suggesting that this variant may not be pathogenic. Computational prediction tools, including splice predictors, and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the c.*119+4759T>C variant is uncertain. ACMG/AMP Criteria applied: PM3_Supporting, PP4, BP4, BP5 (Richards 2015).
New York Genome Center	RCV003228624	SCV003925276	uncertain significance	Dilated cardiomyopathy 1I	2022-08-12	criteria provided, single submitter	clinical testing	The ~42kb duplication on the long arm of chromosome 2 encompasses exons 3 to 9 of DES and exons 1 to 8 (out of 41) of SPEG. Biallelic pathogenic variants in SPEG are associated with Centronuclear myopathy 5 [AR; MIM#615959]. Partial gene duplication in DES has not been reported previously in the literature, ClinVar, or DECIPHER. This gene has not been evaluated by ClinGen Dosage Sensitivity Working Group. Many disease-associated desmin variants cause an accumulation of disorganized intracytoplasmic aggregates containing desmin and other cytoskeletal proteins. Most ofthe known DES pathogenic variants are missense or small in-frame deletions; truncating variants have been more rarely reported in the literature (heterozygous orbiallelic) [PMID: 29926427]. Based on the available evidence, this ~42kb duplication is reported as a Variant ofUncertain Significance.
Medical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia	RCV003388953	SCV003927989	pathogenic	KBG syndrome	2022-07-27	criteria provided, single submitter	clinical testing
Medical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia	RCV003388954	SCV003927990	pathogenic	KBG syndrome	2022-07-27	criteria provided, single submitter	clinical testing
Medical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia	RCV003388955	SCV003927991	pathogenic	KBG syndrome	2022-07-27	criteria provided, single submitter	clinical testing
Medical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia	RCV003388956	SCV003927992	likely pathogenic	KBG syndrome	2022-07-27	criteria provided, single submitter	clinical testing
Medical Genetics Unit, Azienda USL-IRCCS di Reggio Emilia	RCV003388957	SCV003927993	likely pathogenic	KBG syndrome	2022-07-27	criteria provided, single submitter	clinical testing
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV003234736	SCV003932629	pathogenic	Williams syndrome	2023-06-16	criteria provided, single submitter	clinical testing
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV003328726	SCV004035142	pathogenic	X-linked ichthyosis with steryl-sulfatase deficiency		criteria provided, single submitter	clinical testing
Center for Molecular Medicine, Children’s Hospital of Fudan University	RCV003328531	SCV004035252	likely pathogenic	Fructose-biphosphatase deficiency	2022-12-21	criteria provided, single submitter	clinical testing
New York Genome Center	RCV003336017	SCV004046513	likely pathogenic	Aortic aneurysm, familial thoracic 12	2023-04-13	criteria provided, single submitter	clinical testing	The chr15:((71456875_71457375)_71687553) loss is an approximately 230kb deletion on the long arm of chromosome 15. This deletion removes exon 8/18 and flanking intronic sequences of the THSD4 gene (MANE Select transcript NM_024817.3), and is predicted to lead to an out of frame consequence and loss of function via nonsense mediated decay. This variant is absent from population databases (gnomAD SVs v2.1, Database of GenomicVariation) suggesting it is not a common benign variant in the populations represented in those databases. A similar deletion of exon 8 has been reported in ClinVar as a Variant of Uncertain Significance (VarID: 1808966), and to our current knowledge this exact deletion nor similar deletions have been reported in affected individuals in the literature. However, nonsense and frameshift variants upstream and downstream of exon 8 have been reported in individuals in the literature withTAAD, and have been found to segregate with disease in affected families [PMID:32855533]. Given its deleterious nature and absence in population databases, the chr15:((71456875_71457375)_71687553) deletion identified in the THSD4 gene is reported as Likely Pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV003406791	SCV004124534	likely benign	not provided	2022-09-01	criteria provided, single submitter	clinical testing	NBPF11: PM2:Supporting, BP4, BP7; NBPF8: PM2:Supporting, BP4, BP7
CeGaT Center for Human Genetics Tuebingen	RCV003406792	SCV004124535	likely benign	not provided	2022-11-01	criteria provided, single submitter	clinical testing	RP4-565E6.1: BS2
CeGaT Center for Human Genetics Tuebingen	RCV003406793	SCV004124536	likely benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	NBPF12: PM2:Supporting, BP4, BP7
CeGaT Center for Human Genetics Tuebingen	RCV003406794	SCV004124537	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	NBPF12: BP4, BP7
CeGaT Center for Human Genetics Tuebingen	RCV003406795	SCV004124538	likely benign	not provided	2022-06-01	criteria provided, single submitter	clinical testing	NBPF12: BP4, BP7
CeGaT Center for Human Genetics Tuebingen	RCV003408827	SCV004124561	likely benign	not provided	2022-03-01	criteria provided, single submitter	clinical testing	NBPF14: BS1
CeGaT Center for Human Genetics Tuebingen	RCV003408828	SCV004124562	likely benign	not provided	2023-03-01	criteria provided, single submitter	clinical testing	NBPF14: BP4, BS2
CeGaT Center for Human Genetics Tuebingen	RCV003408829	SCV004124563	likely benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	NBPF14: BP4, BS2
CeGaT Center for Human Genetics Tuebingen	RCV003408830	SCV004124564	likely benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	NBPF14: BP4, BS2
CeGaT Center for Human Genetics Tuebingen	RCV003408837	SCV004124571	likely benign	not provided	2023-05-01	criteria provided, single submitter	clinical testing	NBPF16: BP4, BS2
CeGaT Center for Human Genetics Tuebingen	RCV003417250	SCV004126513	likely benign	not provided	2023-02-01	criteria provided, single submitter	clinical testing	MRC1L1: BP4, BP7
CeGaT Center for Human Genetics Tuebingen	RCV003417349	SCV004127625	likely benign	not provided	2022-11-01	criteria provided, single submitter	clinical testing	FAM21B: PM2:Supporting, BP4, BP7
CeGaT Center for Human Genetics Tuebingen	RCV003424838	SCV004129455	likely benign	not provided	2022-05-01	criteria provided, single submitter	clinical testing	HYOU1: BP4, BP7
CeGaT Center for Human Genetics Tuebingen	RCV003425669	SCV004157763	likely benign	not provided	2023-03-01	criteria provided, single submitter	clinical testing	SPATA31A2: BP4, BP7
CeGaT Center for Human Genetics Tuebingen	RCV003435799	SCV004157777	likely benign	not provided	2022-04-01	criteria provided, single submitter	clinical testing	CNTNAP3B: PM2:Supporting, BP4, BP7
CeGaT Center for Human Genetics Tuebingen	RCV003438310	SCV004166339	likely benign	not provided	2022-11-01	criteria provided, single submitter	clinical testing	GAGE2D: BP4, BP7
New York Genome Center	RCV003448557	SCV004176033	likely pathogenic	KBG syndrome	2022-10-03	criteria provided, single submitter	clinical testing	The de novo copy number loss identified here is a ~37.3Kb deletion on the long arm of chromosome 16. This deletion contains ZNF778 and exon 13 of OMIM annotated ANKRD11, which is associated with KBG syndrome (MIM #148050). While the exact deletion identified here has not been previously reported in an affected individual in the literature, similar partial or completely overlapped 16q24.3 microdeletions have been reported in affected KBG syndrome individuals with features of developmental delay, intellectual disability, behavioral issues, speech delay, facial anomalies including macrodontia [PMID: 19920853, 23885231, 22307766, 21654729, 34440431]. The shortest common overlapping region among these reported individuals have been narrowed to ~28.3 kb encompassing the exon 13 of ANKRD11 [PMID: 23463723], suggesting it to be a critical gene for the KBG phenotype. The ~37.3Kb, 16q24.3 de novo deletion identified here has not been observed in the Database of Genomic Variants(DVG) nor in gnomAD SVs(v2.1), suggesting it is not a common benign variant in the populations represented in this database. Based on the available evidence, this ~37.3Kb, de novo copy number loss Chr16:g(89232406_89233606)_(89269724_89268645)del is reported as Likely Pathogenic.
Illumina Laboratory Services, Illumina	RCV003448664	SCV004176306	pathogenic	not provided	2023-05-01	criteria provided, single submitter	clinical testing	This CNV is a 547 kb duplication of 16p11.2 on chromosome 16, (seq[GRCh37]dup(16)(p11.2);NC_000016.9:g.29651786_30199024dup), which is inherited. This CNV affects 27 protein-coding genes and is consistent with the proximal 16p11.2 recurrent region, which is subject to recurrent copy number changes due to the presence of a cluster of low copy repeats (PMID: 20301775). These recurrent breakpoints are sometimes referred to as BP4 and BP5. A few similar duplications have been observed in controls, consistent with the incomplete penetrance and variable phenotypes associated with 16p11.2 duplication (PMID: 21841781). Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448665	SCV004176307	pathogenic	not provided	2023-09-01	criteria provided, single submitter	clinical testing	This CNV is a 1.4 Mb deletion of 17q12 on chromosome 17 (seq[GRCh37]del(17)(q12),;NC_000017.10:g.34814816_36249107del). The CNV encompasses the following protein coding genes: AATF, ACACA, C17orf78, DDX52, DHRS11, DUSP14, GGNBP2, HNF1B, LHX1, MRM1, MYO19, PIGW, SYNRG, TADA2A, and ZNHIT3. The region of the CNV is flanked by segmental duplications that mediate recurrent breakpoints, and overlaps the well described 17q12 recurrent deletion syndrome (PMID: 27929632). This CNV has not been reported in controls. Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448666	SCV004176308	pathogenic	not provided	2023-06-05	criteria provided, single submitter	clinical testing	This CNV is a 3.9 Mb deletion of 3q22.3-q23 on chromosome 3, (seq[GRCh37]del(3)(q22.3q23);NC_000003.11:g.137912620_141811656del) that occurred de novo. This CNV encompasses 28 protein coding genes, including the FOXL2 gene, which is associated with blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES). Additionally, interstitial deletions specifically involving bands 3q22 and 3q23 have been reported in multiple individuals with BPES (PMID: 8291545; 19344873; 20232352; 21934608). This CNV has not been reported in controls. Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448667	SCV004176309	pathogenic	not provided	2023-05-24	criteria provided, single submitter	clinical testing	This CNV is a 9.9 Mb deletion of 4q34.3-q35.2 on chromosome 4, (seq[GRCh37]del(4)(q34.3q35.2); NC_000004.11:g.180937545_190915069del). This CNV constitutes a loss of 38 protein coding genes and has not been reported in controls. Deletions of 4q of varying size and position have been associated with 4q deletion syndrome. Deletions of a similar size and location to this event, including at least three that occurred de novo, have been reported in individuals with developmental delay, craniofacial and skeletal anomalies, congenital malformations, and additional features (PMID: 19344873; 19921640; 22847869). Of note, this event fully encompasses the F11 gene. Individuals with 4q deletions which disrupt the F11 gene may display coagulation defects (PMID: 22159456; 34481514). The CNV also fully encompasses CYP4V2, KLKB1, TRAPPC11, TENM3 and SLC25A4, genes in which loss of function variants are associated with autosomal recessive disorders (PMID: 30013777; PMID: 34648194). Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448668	SCV004176310	pathogenic	not provided	2023-04-13	criteria provided, single submitter	clinical testing	This CNV is a 2 Mb duplication of 17p11.2 on chromosome17, (seq[GRCh37]dup(17)(p11.2); NC_000017.10:g. 16757513_18772328dup). This CNV encompasses 31 protein coding genes, including the RAI1 gene, and overlaps the well-described Potocki-Lupski syndrome (PMID: 17357070; 20188345). The 17p11.2 duplication has not been reported in published controls and is not found in the Genome Aggregation Database (gnomAD SVs version 2.1.). Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448669	SCV004176311	pathogenic	not provided	2023-09-01	criteria provided, single submitter	clinical testing	This CNV is a 1.87 Mb deletion of 5q35.2q35.3 on chromosome 5, (seq[GRCh37]del(5)(q35.2q35.3);NC_000005.9:g.175559209_ 177430432del), that occurred de novo. This event is located near the q terminus of chromosome 5 but does not extend to the telomere. This CNV encompasses 38 protein coding genes, including NSD1, DDX41, and SLC34A1. Haploinsufficiency of NSD1 is a known cause of Sotos syndrome (PMID: 11896389; 17565729; 20301652; 23190751). Microdeletions of 5q35.2q35.3 involving NSD1 have been especially frequently observed in Japanese patients with Sotos syndrome (PMID: 14517949; 20301652). Similar CNVs have not been reported in controls (PMID: 21841781; 24174537). This CNV also encompasses the DDX41 gene, haploinsufficiency of which is associated with DDX41-related hematologic malignancy predisposition syndrome. Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448670	SCV004176312	likely pathogenic	not provided	2023-04-21	criteria provided, single submitter	clinical testing	This CNV is a 94 kb deletion of 15q21.3 on chromosome 15 (seq[GRCh37]del(15)(q21.3); NC_000015.9:g.55525602_ 55619376del). This CNV affects the PIGB, PIGBOS1, and RAB27A protein coding genes. Similar deletions have been reported in ClinVar (VID: 1459351, 1808194) and have been identified in control populations, though not at a frequency that precludes involvement in a disorder with an autosomal recessive inheritance pattern (PMID: 21841781; 24174537). This deletion results in the loss of exons 1-3 of the PIGB gene, which is associated with glycosylphosphatidylinositol deficiency. Loss of function is a known mechanism of this disease (PMID: 31256876), and this CNV is expected to result in an absent or non-functional PIGB gene product. This CNV was identified in trans with a missense variant in the PIGB gene that was classified as a variant of uncertain significance. Based on the available evidence, this CNV is classified as likely pathogenic.
Illumina Laboratory Services, Illumina	RCV003448671	SCV004176313	uncertain significance	not provided	2023-09-01	criteria provided, single submitter	clinical testing	This CNV is a 589 kb duplication of 17p13.1 on chromosome 17 (seq[GRCh37]dup(17)(p13.1);NC_000017.10:g.7709286_8297901dup) that occurred de novo. This CNV encompasses 29 protein-coding genes including CHD3, and has breakpoints in DNAH2 and RNF222. This CNV has not been reported in association with a specific phenotype, nor has it been reported in control cohorts. Small variants in CHD3 have been described in association with Snijders Blok-Campeau syndrome which is characterized by developmental delay, intellectual disability, and characteristic facial features; however, there is limited information on larger duplications encompassing this gene. A duplication which partially overlaps but is larger than this CNV has been reported two siblings with features consistent with Snijders Blok-Campeau syndrome (PMID: 32483341). Based on the available evidence, this CNV is classified as a variant of uncertain significance.
Illumina Laboratory Services, Illumina	RCV003448672	SCV004176314	pathogenic	not provided	2023-05-24	criteria provided, single submitter	clinical testing	This CNV is a 13.0 Mb duplication of 2q36.3-q37.3 on chromosome 2, (seq[GRCh37]dup(2)(q36.3q37.3); NC_000002.11:g.230077026_243049549dup). This CNV constitutes a gain of 124 protein coding genes and has not been reported in controls. Duplications of a similar size and location to this event, including at least six that occurred de novo, have been reported in individuals with intellectual disability, craniofacial and skeletal anomalies, and additional features (PMID: 19344873; 36357380). 2q duplications arise primarily from a parental chromosomal rearrangement associated with the deletion of a partner chromosomal segment (PMID: 19344873; 25851921). Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448673	SCV004176315	pathogenic	not provided	2023-07-25	criteria provided, single submitter	clinical testing	This CNV is a 287 kb deletion of Xp21.1 on chromosome X, (seq[GRCh37]del(X)(Xp21.1); NC_000023.10:g.32448462_32735062del), that is inherited. The breakpoints for this CNV lie within introns 7 and 29 of the DMD gene, resulting in disruption of exons 8-29. These exons code for the actin binding and central rod domains. Smaller deletions in this region have been reported in at least 10 individuals with dystrophinopathies (PMID: 18752307). This CNV has not been reported in controls (PMID: 19344873). Based on the available evidence, this CNV is classified as a pathogenic.
Illumina Laboratory Services, Illumina	RCV003448674	SCV004176316	pathogenic	not provided	2023-08-29	criteria provided, single submitter	clinical testing	This CNV is a 679 kb deletion of 9q34.3, on chromosome 9, (seq[GRCh37]del(9)(q34.3);NC_000009.11:g.140395736_141075109del) that occurred de novo. The CNV encompasses the following protein coding genes: ARRDC1, CACNA1B, DPH7, EHMT1, MRPL41, PNPLA7 and ZMYND19, with a proximal break point disrupting the PNPLA7 gene. Heterozygous deletions of chromosome 9 at 9q34.3 that include at least part, or all of the EHMT1 gene are associated with Kleefstra syndrome (PMID: 20945554). This CNV has not been reported in controls. Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448675	SCV004176317	likely pathogenic	not provided	2023-02-14	criteria provided, single submitter	clinical testing	This CNV is a 71 kb deletion of 2p16.3 on chromosome 2, (seq[GRCh37]del(2)(2p16.3);NC_000002.11:g.51149000_51220337del), which is inherited. This CNV constitutes an in-frame loss of exons 4-6 of the NRXN1 gene. Across a selection of the available literature, similar in-frame deletions of the same exons have been reported in at least 15 individuals with autistic behavior, developmental delays, intellectual disability, dysmorphism, congenital malformations, and other features (PMID: 23495017; PMID: 20468056; PMID: 21827697; PMID: 22617343; PMID: 31932357; PMID: 29165669; PMID: 25408897). In some cases, the deletion was inherited from an unaffected parent. A similar deletion also occurred de novo in at least two cases, although in one individual additional variants were identified that were thought to contribute to the phenotype. Similar deletions have also been reported in several controls (PMID: 21841781; PMID: 24174537; PMID: 23495017), consistent with the reduced penetrance and variable expressivity associated with intragenic deletions of NRXN1. Based on the available evidence, this CNV is classified as likely pathogenic.
Illumina Laboratory Services, Illumina	RCV003448676	SCV004176318	pathogenic	not provided	2023-03-16	criteria provided, single submitter	clinical testing	This CNV is a 16.7 Mb deletion on chromosome 9, (seq[GRCh37]del(9)(q22.2q31.2); chr9:NC_000009.11:92679543_109378847del), of unknown inheritance. This CNV constitutes a deletion encompassing 102 protein coding genes, including the PTCH1 gene and the minimal critical region of the 9q22.3 microdeletion (PMID: 21850767; PMID: 22190277; PMID: 32028043). The TGFBR1 gene is also fully encompassed within the region deleted in this individual, with emerging evidence suggesting that haploinsufficiency of this gene may be associated with multiple self-healing squamous epithelioma, an autosomal dominant predisposition to skin cancer (PMID: 21358634). This CNV has not been reported in controls. Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448677	SCV004176319	pathogenic	not provided	2023-03-21	criteria provided, single submitter	clinical testing	This CNV is a 2.3 Mb deletion of 20p13, on chromosome 20, (seq[GRCh37]del(20)(p13);NC_000020.10:g.61001_2316914del) which occurred de novo. This CNV constitutes a loss encompassing 37 protein coding genes. A total of 11 cases with deletions of 20p13, ranging from 900 kb-2.1 Mb in size and occurring in a de novo state have been reported in the literature (PMID: 19344873; PMID: 20358616; PMID: 22274139). The phenotypic features among these individuals are variable due to the different size of the deletions and include global developmental delay, intellectual disability, short stature, amblyopia, attention deficit hyperactivity disorder, delayed speech and language development, growth abnormality, motor delay, specific learning disability, visual impairment, 2-3 toe syndactyly, abnormality of the skin, adducted thumb, intrauterine growth retardation, postnatal growth retardation, delayed tooth eruption and non-specific dysmorphic features. Of note, this CNV, as well as other reported 20p13 deletions, involve the complete deletion of the CSNK2A1 gene in which intragenic loss of function variants (both missense and truncating variants) are associated with autosomal dominant Okur-Chung neurodevelopmental syndrome characterized by developmental delay, intellectual disability, dysmorphic facial features, behavior issues, hypotonia, seizures, non-specific abnormal brain MRI findings, musculoskeletal defects, short stature, and failure to thrive (PMID: 35679446). This CNV has not been reported in controls. Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448678	SCV004176320	uncertain significance	not provided	2023-05-23	criteria provided, single submitter	clinical testing	This CNV is a 1.2 Mb deletion of 2q11.1-q11.2, on chromosome 2, (seq[GRCh37]del(2)(q11.1q11.2); NC_000002.11:g.96555654_97769352del). This CNV encompasses 35 genes, including 23 protein coding genes, and overlaps the recurrent 2q11.2 deletion region. Patients with similar losses in this region are noted to display highly variable and nonspecific clinical features including developmental delay, intellectual disability, autism spectrum disorder, ADHD, speech delay, craniofacial features, pectus excavatum, and inversion of the foot. Additional features may include hypotonia, encephalopathy, recurrent ear infections, hip joint hypermobility, café au lait spots, aortic coarcation, scoliosis, and other skeletal anomalies (PMID: 19344873; PMID: 19443486; PMID: 26227573). Although segregation was noted in one family with two affected siblings, inheritance from unaffected parents has also been reported (PMID: 19344873; PMID: 26227573). Case-control studies suggest a nominal increase of this deletion in the clinical population (PMID: 25217958). Two similar losses in this region have been reported in controls (PMID: 24174537). Based on the available evidence, this variant is classified as a variant of uncertain significance.
Illumina Laboratory Services, Illumina	RCV003448679	SCV004176321	pathogenic	not provided	2023-05-22	criteria provided, single submitter	clinical testing	This CNV is an approximately 9.7 Mb gain of 15q11.2-q13.3 on chromosome 15, (seq[GRCh37]dup(15)(q11.2q13.3);NC_000015.9:g.22750407_32516333dup) that occurred de novo. The CNV consists of a ~7.6 Mb triplication and a ~1.6 Mb duplication. This region encompasses the Prader Willi/Angelman critical region; duplication or triplication of this imprinted region is associated with the well described maternal 15q duplication syndrome when maternally derived (PMID: 27308687). This chromosomal region is known to be susceptible to rearrangements due to a cluster of five low copy repeats (BP1-BP5); however the exact breakpoints cannot be clearly identified. Together, the triplication and duplication suggest an asymmetric recombination event between BP4 and BP5 resulting in the formation of an isodicentric 15q11.2-q13.2 supernumerary chromosome, idic(15) which includes a region of tetrasomy from the centromere to BP4 and a region of trisomy from BP4 to BP5 (PMIDs: 22585586; 15197683). The CNV has not been reported in published controls and is not present in the Database of Genomic Variants (PMID: 24174537). Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448680	SCV004176322	pathogenic	not provided	2023-04-24	criteria provided, single submitter	clinical testing	This CNV is a 57.7 Mb duplication of 3q23-q29 on chromosome 3, (seq[GRCh37]dup(3)(3q23q29); NC_000003.11:g.140154329_197847235dup) that occurred de novo. This CNV encompasses 284 protein-coding genes and overlaps previously described 3q duplications, occurring as de novo duplications, inversions, or part of an unbalanced translocation. These have been identified in individuals with facial dysmorphism, hirsutism, intellectual disability, developmental delays, poor growth, genitourinary, hand, and foot anomalies, and renal and cardiac defects, among other features (PMID: 27549440; 19344873). Similar duplications have not been described in controls (PMID: 24174537; 21841781). Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448681	SCV004176323	uncertain significance	not provided	2023-08-11	criteria provided, single submitter	clinical testing	This CNV is a 2.2 Mb duplication of 15q26.2-q26.3 on chromosome 15, (seq[GRCh37]dup(15)(q26.2-26.3);NC_000015.9:g.96345673_98563904dup) that occurred de novo. This CNV encompasses two protein coding genes, ARRDC4 and NR2F2. Duplication of a similar region is not common in controls and has not, to our knowledge, been described in the peer-reviewed literature. However, a larger, 3.6 Mb duplication affecting the same protein coding genes has been classified as likely pathogenic in ClinVar (VID 395722). In addition, a patient in the DECIPHER database, 266158, whose phenotype includes triangular face, brachydactyly, 5th finger clinodactyly, lower limb hypertrophy, abnormal repetitive mannerisms, and intellectual disability, is reported to have inherited a 1.85 Mb duplication of 15q26.3 including the NR2F2 gene from an unaffected parent. This individual also carried additional inherited CNVs, including a 5.0 Mb terminal deletion of 15q26.3 distal to the duplication. Based on the available evidence, this CNV is classified as a variant of uncertain significance.
Illumina Laboratory Services, Illumina	RCV003448682	SCV004176324	pathogenic	not provided	2023-09-15	criteria provided, single submitter	clinical testing	This CNV is a 4.6 Mb deletion of 17p13.3-p13.2 on chromosome 17, (seq[GRCh37]del(17)(p13.3-p13.2);NC_000017.10:g.2_4611147del) that occurred de novo. The CNV encompasses 82 protein coding genes and overlaps the well-described Miller-Dieker syndrome (MDS). This CNV results in the deletion of the MDS telomeric critical region including the PAFAH1B1 gene (previously known as LIS1), YWHAE (previously known as 14-3-3-epsilon), and many other contiguous genes (PMID: 12621583). This CNV has not been reported in controls (PMID: 24174537). Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448683	SCV004176325	pathogenic	not provided	2023-08-15	criteria provided, single submitter	clinical testing	This CNV is a 3.8 Mb deletion of 15q26.3 on chromosome 15, seq[GRCh37]del(15)(q26.3), NC_000015.9:g.98565904_102400021del, which is found in a de novo state. This CNV encompasses 21 protein coding genes, including the IGF1R, ALDH1A3, LRRK1, CHSY1, SELENOS, SNRPA1, and PCSK6 genes. Deletions of 15q26.3, both including and distal to IGF1R, have been reported in more than 30 individuals with phenotypes that include poor pre- or postnatal growth, developmental delay or intellectual disability, facial dysmorphism, congenital heart defects, skeletal anomalies, and microcephaly (PMID: 19344873; 27826649; 29165669; 37434556). In some cases, the deletions were shown to occur de novo. A microdeletion of 15q26.3 affecting the IGF1R gene has also been shown to segregate with short stature in one three-generation family (PMID: 19955558). Similar deletions are not common in controls. Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448684	SCV004176326	likely pathogenic	not provided	2023-05-04	criteria provided, single submitter	clinical testing	This CNV is a 121 kb deletion of 2q32.2 on chromosome 2 (seq[GRCh37]del(2)(q32.2), NC_000002.11:g.191078575_191199676del). The CNV encompasses exons 1-11 of the HIBCH gene and is predicted to result in loss of protein function. To our knowledge, this CNV has not been reported in individuals with primary mitochondrial disorder. The 2q32.2 has not been reported in healthy controls. Based on the available evidence, this CNV is classified as likely pathogenic.
Illumina Laboratory Services, Illumina	RCV003448685	SCV004176327	likely pathogenic	not provided	2023-03-22	criteria provided, single submitter	clinical testing	This CNV is a 10 kb duplication of 15q21.1 on chromosome 15, (seq[GRCh37]dup(15)(q21.1), chr15:g.48724466_48734658dup). The breakpoints of this CNV lie within the FBN1 gene, in introns 49 and 55, resulting in duplication of exons 50-55. These exons encode for the calcium binding EGF domains, which is a critical domain for protein function and harbors clinically significant variants (PMID: 27138491). This CNV has not been reported in controls. Based on the available evidence, this CNV is classified as likely pathogenic.
Illumina Laboratory Services, Illumina	RCV003448686	SCV004176328	pathogenic	not provided	2023-07-25	criteria provided, single submitter	clinical testing	This CNV is a 33 kb deletion of 22q11.21 on chromosome 22 (seq[GRCh37]dup(22)(q11.21);NC_000022.10:g.20028654_20061617del). This CNV encompasses exons 3-9 of the TANGO2 gene. An ~34 kb deletion encompassing exons 3-9 is the most common variant reported in association with TANGO2 deficiency (PMID: 29369572). It is most common in the non-Finnish/European population, where it has an estimated allele frequency of 0.14% (PMID: 29369572; 26805782). Across a selection of the available literature, homozygous deletion of TANGO2 exons 3-9 has been reported in at least 12 unrelated patients (PMID: 26805781; 26805782; 31276219; 30245509; 19344873). The deletion has also been identified in trans with at least five other TANGO2 variants in individuals with a phenotype consistent withTANGO2 deficiency and to segregate with the phenotype in multiple families in the literature. This variant was found in a homozygous state. Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448687	SCV004176329	uncertain significance	not provided	2023-09-15	criteria provided, single submitter	clinical testing	This CNV is a 1.2 Mb duplication of 17q25.3, on chromosome 17, seq[GRCh37]dup(17)(q25.3), NC_000017.10:g.79928042_8115212dup, which is found in a de novo state. This CNV encompasses 29 protein coding genes. Individuals with 17q25.3 duplication of varying sizes presented with abnormal brain imaging, eye and muscular/skeletal abnormalities, ADHD, and psychiatric disorders (PMID: 26070612). A partially overlapping duplication in this region was inherited from an unaffected parent in a proband with developmental delay, intellectual disability, low muscle tone, posterior cerebellar artery syndrome, and dysmorphic features (PMID: 37430334). At least one slightly smaller CNV gain encompassing most of this region has been reported in controls (PMID: 24174537). Based on the available evidence, this CNV is classified as a variant of uncertain significance.
Illumina Laboratory Services, Illumina	RCV003448688	SCV004176330	uncertain significance	not provided	2023-09-12	criteria provided, single submitter	clinical testing	This CNV is a 19.5 kb deletion of 15q11.2 on chromosome 15, seq[GRCh37]del(15)(q11.2), NC_000015.9:g.25064951_25084452del. This CNV encompasses an upstream region, exon one and part of the first intron of the longest (canonical) transcript of the SNRPN gene, NM_022806.3. This region does not overlap with the Prader-Willi syndrome (PWS) imprinting center (IC) (PMID: 9973278; 20301505; 22237428; 28554868; 29437285). A similar deletion, which was paternally inherited, has been described in an individual with features consistent with PWS (PMID: 27659333). Similar deletions have been reported in controls but not demonstrated to be paternally derived (PMID: 21841781; 24174537). A similar deletion has been observed at a frequency of 0.00965 in the African/African American population of the Genome Aggregation Database (gnomAD SVs version 2.1). Based on the available evidence, this CNV is classified as a variant of uncertain significance.
Illumina Laboratory Services, Illumina	RCV003448689	SCV004176331	pathogenic	not provided	2023-05-05	criteria provided, single submitter	clinical testing	This CNV is a 980 kb deletion of 20p13 on chromosome 20, seq[GRCh37]del(20)(p13), NC_000020.10:g.61001_1041262del, which is found in a de novo state. This CNV encompasses 21 protein coding genes, including the CSNK2A1, SOX12, NRSN2 genes. Similar 20p13 microdeletions, including in a de novo state, have been reported in individuals with features including developmental delay, learning and intellectual disability, short stature, microcephaly, seizures, and variable facial dysmorphism (PMID: 19344873; 24019301; 31087544; 33678341). Similar CNVs have not been observed in controls (PMID: 21841781; 24174537). Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448690	SCV004176332	uncertain significance	not provided	2023-03-09	criteria provided, single submitter	clinical testing	This CNV is a 1.8 Mb duplication of 8p21.3, on chromosome 8, (seq[GRCh37]dup(8)(p21.3), chr8:g.20868762_22701502dup), which is found in a de novo state. This CNV constitutes a gain encompassing 26 protein coding genes, including full duplication of the BMP1 gene. Variants in the BMP1 gene are known to cause an autosomal recessive form of osteogenesis imperfecta (PMID: 33085247). However, there is no literature evidence to support triplosensitivity as a mechanism of disease for this gene. Patients with similar duplications in this region have not been reported in the peer-reviewed literature. A few similar sized de novo CNVs of uncertain significance or unconfirmed parentage with non-specific phenotypes have been reported in the DECIPHER database (PMID: 19344873). This CNV has not been reported in controls. Based on the available evidence, this CNV is classified as a variant of uncertain significance.
Illumina Laboratory Services, Illumina	RCV003448691	SCV004176333	uncertain significance	not provided	2023-05-24	criteria provided, single submitter	clinical testing	This CNV is a 609 kb duplication of Xp11.22 on chromosome X, (seq[GRCh37]dup(X)(Xp11.22); NC_000023.10:g.54054624_54663870dup). This CNV encompasses the following six protein coding genes: FAM120C, FGD1, GNL3L, TSR2, WNK3, PHF8. The breakpoints lie within intron 2 of PHF8 and in an intergenic region. Loss of function variants in PHF8 are associated with an X-linked neurodevelopmental disorder in which males show a spectrum of developmental delay, speech delay, intellectual disability, and variable craniofacial features (PMID: 35469323). Duplications of a similar size and location to this event have been reported in individuals with variable features and have not been reported in controls (PMID: 19344873). This event also fully encompasses FGD1, a gene in which loss of function variants are associated with X-linked Aarskog-Scott syndrome. Based on the available evidence, this CNV is classified as a variant of uncertain significance.
Illumina Laboratory Services, Illumina	RCV003448692	SCV004176334	pathogenic	not provided	2023-03-16	criteria provided, single submitter	clinical testing	This CNV is a 34.7 Mb duplication of 12p on chromosome 12, (seq[GRCh37]dup(12)(p13.33p11.1); chr12:g.188053_34856694dup), which is apparently mosaic. The CNV constitutes a gain encompassing 280 protein coding genes, and overlaps the critical region associated with both mosaic 12p trisomy and Pallister-Killian syndrome. This critical region is located at 12p13.31 and contains the candidate genes ING4, CHD4, and MAGP2, though causality has not yet been ascribed to a specific gene (PMID: 34073526). Similar mosaic CNVs have been reported in individuals with developmental delays, hypotonia, digital anomalies, congenital heart defects, and variable craniofacial features (PMID: 16502429; PMID: 31913574). The 12p duplication has not been reported in published controls. Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448693	SCV004176335	pathogenic	not provided	2023-08-17	criteria provided, single submitter	clinical testing	This CNV is a 31 Mb duplication of 8p23.1-p11.1 on chromosome 8, seq[GRCh37]dup(8)(p23.1p11.1), NC_000008.10:g.12530550_43483193dup, which is found in a de novo state. This CNV encompasses 180 protein coding genes. Duplications of 8p of a similar size and location to this event have been reported in individuals with features that include developmental and motor delay, neonatal feeding problems, hypotonia, structural brain abnormalities, and facial dysmorphism (PMID: 8256810; 8533823; 8599364; 19344873; 29165669; https://doi.org/10.1016/j.genrep.2017.11.006). In many cases, the duplication was shown to arise de novo. In addition, duplication of 8p was accompanied by deletion of 8p23.1 to 8pter in many individuals. This CNV has not been reported in controls. Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448694	SCV004176336	pathogenic	not provided	2023-05-23	criteria provided, single submitter	clinical testing	This CNV is a 7.2 Mb deletion of 3p26.3-p26.1 on chromosome 3, (seq[GRCh37]del(3)(3p26.3p26.1), NC_000003.11:g.61434_7264917del). This CNV constitutes a loss of 14 protein coding genes and has not been reported in controls. Deletions of a similar size occurring either de novo or as a result of a balanced translocation in an unaffected parent, have been reported in multiple individuals with developmental abnormalities and dysmorphic features (PMID: 19344873). Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448695	SCV004176337	pathogenic	not provided	2023-05-08	criteria provided, single submitter	clinical testing	This CNV is a 1.3 Mb deletion of 17p12 on chromosome 17 (seq[GRCh37]del(17)(p12); NC_000017.10:g.14098446_15442637del). This CNV overlaps the well-described 17p12 deletion associated with autosomal dominant hereditary neuropathy with liability to pressure palsies (HNPP) and encompasses the following protein coding genes: TVP23C-CDRT4, CDRT15, TEKT3, PMP22, CDRT4, TVP23C, HS3ST3B1, COX10. The 17p12 region is prone to rearrangements due to the presence of low copy repeats, referred to as the proximal CMT1A-REP and distal CMT1A-REP (PMID: 30258273). This deletion fully encompasses the PMP22 gene, which has been identified as the main candidate underlying HNPP. PMP22 encodes the peripheral myelin protein 22 which is associated with myelin organization in the peripheral nervous system (PMID: 23224996; 24697164). Deletions of approximately 1.4 Mb at 17p12 have been described in approximately 85-90% of individuals with clinical evidence of HNPP (PMID: 24646194). Based on the collective evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448696	SCV004176338	pathogenic	not provided	2023-06-01	criteria provided, single submitter	clinical testing	This CNV is a 16.3 Mb deletion of 9p24.3-p22.3 on chromosome 9, seq[GRCh37]del(9)(p24.3p22.3), NC_000009.11:g.204064_16456192del. The CNV encompasses 49 protein coding genes including the NFIB gene and overlaps the proposed critical regions of the well described 9p deletion syndrome (PMID: 35047865). The NFIB gene encodes nuclear factor 1 B, a transcription factor that regulates mammalian development. Haploinsufficiency of NFIB is associated with acquired macrocephaly with impaired intellectual development (MIM 600728). The CNV has not been reported in published controls and is not present in the Database of Genomic Variants (PMID: 24174537). Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448697	SCV004176339	pathogenic	not provided	2023-04-25	criteria provided, single submitter	clinical testing	This CNV is a 10.4 Mb deletion of 15q15.1-q21.2, on chromosome 15, (seq[GRCh37]del(15)(q15.1q21.2);NC_000015.9:g.41321409_51718601del) that occurred de novo. This CNV encompasses 106 protein coding genes, including the FBN1 gene. Whole gene deletions of FBN1 are known to cause Marfan syndrome, which is a connective tissue disorder primarily characterized by ocular, skeletal and cardiovascular system involvement (PMID: 21063442; GeneReviews NBK1335; PMID: 34475413). Several de novo deletions overlapping 15q15.1-q21.2 regions have been reported in affected individuals (PMID: 19344873). This CNV has not been reported in controls (PMID: 24174537). Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448698	SCV004176340	uncertain significance	not provided	2023-08-24	criteria provided, single submitter	clinical testing	This CNV is a 5.7 Mb deletion of 5q21.3-q22.2 on chromosome 5, seq[GRCh37]del(5)(q21.3q22.2), NC_000005.9:g.106137712_111825745del. This CNV encompasses 13 protein-coding genes, with breakpoints in intergenic regions. There is limited evidence for an association of the CAMK4 gene with an autosomal dominant complex neurodevelopmental disorder (PMID: 33211350) and two genes, EFNA5 and FBLX17, are predicted to be intolerant to loss-of-function variation but to date do not have enough evidence for an association with disease. The SLC25A46 gene is associated with hereditary motor and sensory neuropathy type 6B and pontocerebellar hypoplasia type 1E, both of which follow an autosomal recessive pattern of inheritance. Similar deletions have been identified in two patients with syndromic neurodevelopmental phenotypes (PMID 19344873; 22970919). This CNV has not been reported in controls. Based on the available evidence, this CNV is classified as a variant of uncertain significance.
Illumina Laboratory Services, Illumina	RCV003448699	SCV004176341	pathogenic	not provided	2023-05-12	criteria provided, single submitter	clinical testing	This CNV is a 473 kb deletion of 15q11.2 on chromosome 15, seq[GRCh37]del(15)(q11.2), NC_000015.9:g.22750407_23223112del. This CNV encompasses the following protein coding genes: CYFIP1, NIPA1, NIPA2, and TUBGCP5. While the precise breakpoints of this CNV cannot be determined due to the presence of low copy repeats on both ends, their general locations correspond well with the recurrent BP1-BP2 breakpoints known to be associated with 15q11.2 microdeletion syndrome which is known to have low penetrance (PMID: 25689425). Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448700	SCV004176342	pathogenic	not provided	2023-08-18	criteria provided, single submitter	clinical testing	This CNV is a 120 kb deletion of 2q13 on chromosome 2, seq[GRCh37]del(2)(q13), NC_000002.11:g.112687864_112808213del, which encompasses exons 3-19 of the MERTK gene and is predicted to disrupt the MERTK gene product. One of the breakpoints lies within intron 2 and the other in an intergenic region. Deletion of exons 3-19 has been reported in a homozygous state in an individual with cone-rod dystrophy (CRD) (PMID: 26103963). Additionally, this deletion is reported with a missense variant in an individual with retinal dystrophy, and with a splice region variant in an individual with retinitis pigmentosa (unconfirmed diagnosis). However, the phase of the variants identified in these individuals was not confirmed (PMID: 29074561; 32783370). Smaller deletions in this region have also been reported in individuals with retinopathies (PMID: 29659094). A similar deletion has been observed at a frequency of 0.001468 in the African/African American population of the Genome Aggregation Database (gnomAD SVs version 2.1). Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448701	SCV004176343	uncertain significance	not provided	2023-06-07	criteria provided, single submitter	clinical testing	This CNV is a 1.2 Mb deletion of 2q31.3, on chromosome 2, seq[GRCh37]del(2)(q31.3), NC_000002.11:g.181456042_182687758del, which is found in a de novo state. This CNV encompasses the following protein coding genes: CERKL, ITGA4, NEUROD1, UBE2E3. A similar overlapping deletion has been reported in an individual with autism and global developmental delay (PMID: 19344873). This CNV has not been reported in controls. Based on the available evidence, this CNV is classified as a variant of uncertain significance.
Illumina Laboratory Services, Illumina	RCV003448702	SCV004176344	uncertain significance	not provided	2023-06-22	criteria provided, single submitter	clinical testing	This CNV is a 259 kb duplication of 2q33.1 on chromosome 2, seq[GRCh37]dup(2)(q23.1), NC_000002.11:g.200227328_200486417dup. This CNV encompasses part of one protein coding gene, SATB2, and duplicates the first 7 exons of this gene. One breakpoint lies in intron 7 of SATB2 and another lies in intron 1 of the LINC01877 gene which is a non protein-coding gene. Smaller duplications of SATB2 that duplicate either some internal exons or the first several exons of this gene, and which overlap this duplication, have been reported in the peer-reviewed literature in individuals with neurodevelopmental phenotypes (PMID: 25118029; 19344873). This CNV has not been reported in controls. Based on the available evidence, this CNV is classified as a variant of uncertain significance.
Illumina Laboratory Services, Illumina	RCV003448703	SCV004176345	pathogenic	not provided	2023-04-03	criteria provided, single submitter	clinical testing	This CNV is a 9.9 Mb terminal deletion of 3p26.3-p25.3 on chromosome 3, (seq[GRCh37]del(3)(p26.3-p25.3); chr3:g.61435_9944653del), which is found in a de novo state. This CNV constitutes a deletion encompassing 36 protein coding genes, including the SETD5 gene, and overlaps the well-described 3p deletion syndrome. Similar deletions have been reported in affected individuals (PMID: 19760623; PMID: 33643973) and have not been described in controls. The clinical presentation may be dependent on the size and location of the deletion. Analysis into the critical regions causative for certain associated clinical features have produced several genes of interest, although their contributions are not well defined. Most deletions occur de novo or as part of an unbalanced translocation, but autosomal dominant inheritance has also been observed (PMID: 19760623; PMID: 25138099; PMID: 28402723; PMID: 33643973; PMID: 33936696). Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448704	SCV004176346	pathogenic	not provided	2023-05-23	criteria provided, single submitter	clinical testing	This CNV is a 21.3 Mb duplication of 3q26.32-q29 on chromosome 3, (seq[GRCh37]dup(3)(3q26.32q29), NC_000003.11:g.176412210_197847235dup). This CNV constitutes a gain of 144 protein coding genes and has not been reported in controls. De novo duplications of a similar size and location to this event have been reported in individuals with global developmental delay, motor delay and dysmorphic features (PMID: 19344873). Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448705	SCV004176347	pathogenic	not provided	2023-09-13	criteria provided, single submitter	clinical testing	This CNV is a 1.27 Mb deletion of 18q21.2-q21.31 on chromosome 18, seq[GRCh37]del(18)(q21.2q21.31), NC_000018.9:g.53218644_54488400del, which is found in a de novo state. The CNV encompasses three protein-coding genes, including exons 1-3 of the TCF4 gene. Deletions overlapping this region, including those with partial or complete deletion of the TCF4 gene, have been associated with Pitt-Hopkins syndrome (PMID: 27132474; 35189377). The 18q21.2-q21.31 deletion has not been reported in controls. Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448706	SCV004176348	pathogenic	not provided	2023-03-10	criteria provided, single submitter	clinical testing	This CNV is a 1.4 Mb deletion of 17q11.2 on chromosome 17 (seq[GRCh37]del(17)(q11.2); chr17:g.29000371_30367382del), which is found in a de novo state. This CNV constitutes a deletion encompassing 14 protein-coding genes, including NF1, and overlaps the well-described NF1 microdeletion syndrome, a severe manifestation of neurofibromatosis type 1 (NF1). Four types of large NF1 deletions (type-1, -2, -3 and atypical) have been identified. These are distinguishable by their size, breakpoint location, and the number of genes within the deleted region. The most common are the type-1 deletions which are usually around 1.4 Mb. This CNV has not been reported in controls. Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448707	SCV004176349	pathogenic	not provided	2023-08-17	criteria provided, single submitter	clinical testing	This CNV is a 7.1 Mb deletion of 8p23.3-p23.1 on chromosome 8, seq[GRCh37]del(8)(p23.3p23.1), NC_000008.10:g.162266_7226691del, which is found in a de novo state. This CNV encompasses 30 protein coding genes. Distal 8p deletions that vary in size and location within 8p23 have been reported in multiple individuals with features that include intellectual disability, developmental delay, motor impairment, behavioral differences, congenital heart defects, microcephaly, and mild facial dysmorphism (PMID: 1619636; 19344873; 29165669; 33925474). In some cases, the deletions were confirmed to have occurred de novo. The FBXO25, DLGAP2, CLN8, ARHGEF10, and MYOM2 genes have been proposed as critical genes (PMID: 20459802; 28901431; 33925474). This CNV has not been reported in controls. Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448708	SCV004176350	pathogenic	not provided	2023-09-04	criteria provided, single submitter	clinical testing	This CNV is a 2.1 Mb deletion of 19q13.11-19q13.12 on chromosome 19, (seq[GRCh37]del(19)(q13.11q13.12); NC_000019.9:g.35225414_37357598del) that occurred de novo. The CNV encompasses 75 protein-coding genes, including an entire deletion of the KMT2B gene. Overlapping heterozygous interstitial microdeletions at 19q13.11-19q13.12 have been associated with complex progressive childhood-onset dystonia (PMID: 27992417; 29697234; 33150406). The 19q13.11-19q13.12 deletion has not been reported in controls. Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448709	SCV004176351	uncertain significance	not provided	2023-08-24	criteria provided, single submitter	clinical testing	This CNV is a 5.1 Mb deletion of q12.1-q13.1 on chromosome 5, (seq[GRCh37]del(5)(q12.1q13.1);NC_000005.9:g.62757224_67825254del). This CNV encompasses 19 protein-coding genes, with breakpoints in intergenic regions. The CNV includes the PIK3R1 gene which is associated with SHORT syndrome and immunodeficiency 36, both of which follow an autosomal dominant pattern of inheritance (MIM #269880; MIM #616005). Several genes in this region are predicted to be intolerant to loss-of-function variation but to date do not have evidence for association with disease. The CWC27 gene is associated with retinitis pigmentosa with or without skeletal anomalies which follows an autosomal recessive pattern of inheritance (MIM #250410); however, no other candidate variants were identified in this gene. Similar deletions of this region have been identified in several patients with phenotypes including syndromic intellectual disability, macrocephaly, epilepsy, and restricted growth (PMID 19344873; 23262338; 26138022; 28611550). This CNV has not been reported in controls. Based on the available evidence, this CNV is classified as a variant of uncertain significance.
Illumina Laboratory Services, Illumina	RCV003448710	SCV004176352	pathogenic	not provided	2023-06-06	criteria provided, single submitter	clinical testing	This CNV is a 32.81 Mb duplication of 11q22.2-q25 on chromosome 11, (seq[GRCH37]dup(11)(q22.2q25);NC_000011.9:g.102134973_134945611dup) that occurred de novo. This CNV encompasses 271 protein coding genes and overlaps the well described partial trisomy 11q syndrome. This CNV has not been reported in published controls and is not present in Database of Genomic Variants (PMID: 24174537). Based on the available evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448711	SCV004176353	pathogenic	not provided	2023-06-12	criteria provided, single submitter	clinical testing	This CNV is a 1.68 Mb deletion of Xp22.31 on the X chromosome, (seq[GRCh37]del(X)(p22.31); chrX:g.6453342_8137213del), which is inherited. This event encompasses at least six genes, including MIR4767, MIR651, PNPLA4, PUDP, STS and VCX. Similar CNVs have been reported in several affected males in the literature (PMID: 17113756; 18076704; 23791652; 23807007). Based on the collective evidence, this CNV is classified as pathogenic.
Illumina Laboratory Services, Illumina	RCV003448712	SCV004176354	pathogenic	not provided	2023-05-11	criteria provided, single submitter	clinical testing	This CNV is a 17 kb deletion of Xq28 on chromosome X, (seq[GRCh37]del(X)(q28);NC_000023.10:g.149823254_149839805del). This CNV affects a single protein coding gene and constitutes an in-frame deletion of exons 11-14 of the MTM1 gene. The deletion includes approximately 40% of the phosphatase domain and is expected to disrupt the function of the gene product. Up to 7% of MTM1 variants associated with X-linked centronuclear myopathy are deletions involving one or more exons, and such deletions frequently cause severe disease (PMID: 10790201; 11793470; 12522554; 15145343; 15725586). An in-frame deletion of exon 13 has been reported in a patient with biopsy-proven centronuclear myopathy whose clinical presentation was described as severe (PMID: 11793470). Based on the available evidence, this CNV is classified as pathogenic for X-linked centronuclear myopathy.
Center for Statistical Genetics, Columbia University	RCV003459046	SCV004183568	likely pathogenic	Bilateral polymicrogyria	2023-12-18	criteria provided, single submitter	research
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003477097	SCV004219316	pathogenic	not provided	2023-05-16	criteria provided, single submitter	clinical testing	This variant is predicted to disrupt the translation reading frame of the ATM mRNA and result in the premature termination of ATM protein synthesis. This deletion is also known as IVS63del16kb or a deletion of exons 64-65. In the published literature, similar deletions of exons 62-63 in the ATM gene have been reported in women affected with breast and/or ovarian cancer (PMIDs: 25428789 (2015), 26681312 (2015), 30086788 (2018), 30322717 (2018), 32206661 (2020), 33919281 (2021)) and in multiple families affected with ataxia-telangiectasia (PMIDs: 9443866 (1998), 9792409 (1998), 21665257 (2011), 22006793 (2012), 25122203 (2014), 25614872 (2014), 33547824 (2021)). Based on the available information, this variant is classified as pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003477129	SCV004220550	uncertain significance	not provided	2023-08-03	criteria provided, single submitter	clinical testing	This test has identified a one copy duplication of a genomic region which encompasses exons 62-63 (c.8851_*3591) of the ATM gene. We are unable to determine if this duplication occurs in tandem with exons 62-63 of the ATM gene or is inserted elsewhere in the genome. In the published literature, a similar duplication of exons 62-63 in the ATM gene has been reported in an individual with Ataxia-Telangiectasia who also had a truncating ATM variant (PMID: 25122203 (2014)). Similar duplication variants were also identified in individuals affected with breast cancer as well as in reportedly healthy individuals (PMID: 36551643 (2022)). This variant has also been described in cancer-free women over age 70 (FLOSSIES database (https://whi.color.com/)). The frequency of this variant in the general population (Genome Aggregation Database, https://gnomad.broadinstitute.org) is uninformative in the assessment of its pathogenicity. Based on the available information, we are unable to determine the clinical significance of this variant.
Athena Diagnostics	RCV003482498	SCV004229159	uncertain significance	not provided	2023-08-14	criteria provided, single submitter	clinical testing	Available data are insufficient to determine the clinical significance of the variant at this time. This duplication includes the entire coding sequence of the ATM gene. Due to limitations of this analysis, the exact size and insertion point of the duplication is unknown. Any potential impact of this duplication on the ATM gene cannot be determined. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org).
Athena Diagnostics	RCV003482608	SCV004229451	pathogenic	not provided	2022-12-22	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Similar deletions of exons 47-50 have been primarily reported in patients with DMD, and also at least one with BMD (PMID: 26081009). Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV003482616	SCV004229472	pathogenic	not provided	2023-04-25	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Similar deletions of exons 43-50 have been identified in multiple unrelated individuals with DMD. Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV003482623	SCV004229479	pathogenic	not provided	2023-01-05	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)). A similar deletion of exons 31-50 has been identified in at least one male with DMD.
Athena Diagnostics	RCV003482629	SCV004229488	likely pathogenic	not provided	2023-05-18	criteria provided, single submitter	clinical testing	This deletion is expected to result in the loss of a functional protein in a gene for which loss of protein function associates with disease. Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV003482634	SCV004229498	pathogenic	not provided	2022-04-05	criteria provided, single submitter	clinical testing	This deletion variant is predicted to maintain the open reading frame. However, due to the altered protein length, it is expected to severely disrupt protein function. Similar deletions of exons 45-47 have been reported primarily in patients with Becker muscular dystrophy (BMD), and also in individuals with Duchenne muscular dystrophy (DMD; PMID: 19937601, 17259292, 25972034, 28610567, 31443951 ). Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV003482644	SCV004229509	pathogenic	not provided	2022-10-21	criteria provided, single submitter	clinical testing	This deletion variant is predicted to maintain the open reading frame. However, due to the altered protein length, it is expected to severely disrupt protein function. A similar deletion of exons 42-44 has been identified in at least one individual with clinical features of BMD, and in individuals where the type of dystrophinopathy was not specified. Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV003482649	SCV004229521	pathogenic	not provided	2023-04-11	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. A similar deletion of exon 7 has been identified in multiple individuals with Duchenne muscular dystrophy (DMD). Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV003482652	SCV004229528	pathogenic	not provided	2023-03-20	criteria provided, single submitter	clinical testing	This deletion maintains the transcript's reading frame but is expected to disrupt protein function. Similar deletions of exons 8 to 9 have been identified in multiple unrelated individuals with spastic paraplegia and appears to segregate with disease in at least one family (PMID: 19423133, 25065914, 30476002). Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV003482655	SCV004229534	pathogenic	not provided	2023-06-20	criteria provided, single submitter	clinical testing	Similar deletions of exon 16 have been identified in multiple unrelated individuals with clinical features associated with this gene. This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)). The variant is located in a region that is considered important for protein function and/or structure.
Athena Diagnostics	RCV003482658	SCV004229541	pathogenic	not provided	2022-09-22	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. A similar variant has been identified in at least one individual with clinical features associated with this gene. Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV003482659	SCV004229546	pathogenic	not provided	2023-07-13	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. A similar variant has been identified in at least one individual with clinical features associated with this gene. Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV003482661	SCV004229554	pathogenic	not provided	2023-08-17	criteria provided, single submitter	clinical testing	This deletion includes the entire coding sequence of the TSC2 gene. Due to limitations of this analysis, the exact size of the deletion is unknown and may involve additional genes. A similar variant has been identified in at least one individual with clinical features associated with this gene. Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV003482675	SCV004229605	pathogenic	not provided	2022-10-24	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. A similar deletion of exon 62 has been identified in multiple males with DMD. Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Athena Diagnostics	RCV003482858	SCV004230014	pathogenic	not provided	2023-06-13	criteria provided, single submitter	clinical testing	This variant is expected to result in the loss of a functional protein. Similar deletions of exon 46-52 have been reported in multiple unrelated individuals with DMD, and also in at least one individual with BMD (PMID: 29976999). Similar variants have not been reported in large, multi-ethnic general populations (Genome Aggregation Database (gnomAD), Cambridge, MA (URL: http://gnomad.broadinstitute.org)).
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV003494597	SCV004232719	pathogenic	Osteogenesis imperfecta type I	2024-01-28	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV003494598	SCV004232720	pathogenic	Osteogenesis imperfecta type I	2024-01-28	criteria provided, single submitter	clinical testing
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV003494599	SCV004232721	pathogenic	Tricho-dento-osseous syndrome; Osteogenesis imperfecta type I	2024-01-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003885695	SCV004699432	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	NBPF14: BP4, BS2
CeGaT Center for Human Genetics Tuebingen	RCV003884162	SCV004702809	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	ASAH2C: PP2, BS2
Illumina Laboratory Services, Illumina	RCV003985128	SCV004801405	pathogenic	not provided	2021-04-28	criteria provided, single submitter	clinical testing	This CNV is a 449 kb deletion of 1q21.1 on chromosome 1 (seq[GRCh37]del(1)(q21.1); chr1:g.145382448_145831727del) that is inherited. The exact break points of this event could not be resolved due to the presence of low complexity sequences both centromeric and telomeric to this event. This CNV constitutes a loss encompassing at least 17 genes, including RBM8A, and overlaps with deletions reported in at least 50 probands with TAR syndrome (Klopocki et al. 2007; Albers et al. 2012). Based on the evidence, this CNV is classified as pathogenic for TAR syndrome.
Illumina Laboratory Services, Illumina	RCV003985129	SCV004801406	pathogenic	not provided	2021-08-21	criteria provided, single submitter	clinical testing	This CNV is a 52 kb deletion of 7p22.1 on chromosome 7, (seq[GRCh37]del(7)(p22.1),NC_000007.13:g.6028194_6080194del) of unknown inheritance. This CNV encompasses four protein-coding genes, ANKRD61, AIMP2, EIF2AK1, and PMS2. This CNV results in total loss of the AIMP2 gene. This individual also carries a frameshift variant in AIMP2 in trans with the CNV. Biallelic loss of function variants in AIMP2 have been associated with an autosomal recessive form of hypomyelinating leukodystrophy (PMIDs: 29215095; 35140751). Similarly sized CNVs have not been observed in controls. Based on the available evidence, this CNV is classified as pathogenic for hypomyelinating leukodystrophy.
Illumina Laboratory Services, Illumina	RCV003985130	SCV004801407	pathogenic	not provided	2023-07-27	criteria provided, single submitter	clinical testing	This CNV is a 4.2 kb deletion of the mitochondrial DNA from m.10775 - 14941del detected at a heteroplasmic fraction of 77-80% in blood. This variant was not detected in the blood of the mother. This deletion encompasses the following genes - MT-ND4, MT-TH, MT-TS2, MT-TL2, MT-ND5, MT-ND6, MT-TE and MT-CYB. For three of these genes, MT-ND4, MT-ND5 and MT-ND6, loss of function is implicated as the mechanism of disease. Similar deletions have been observed in several patients in the literature (Rotig et al. 1990; Larsson and Holme 1992; Chinault et al. 2009; Khasawneh et al. 2018; Rocha et al. 2018). Based on the available evidence, this variant is classified as pathogenic for primary mitochondrial disease.
Ambry Genetics	RCV004460872	SCV004957996	uncertain significance	not specified	2023-11-14	criteria provided, single submitter	clinical testing	The c.14905G>A (p.G4969R) alteration is located in exon 98 (coding exon 98) of the SSPO gene. This alteration results from a G to A substitution at nucleotide position 14905, causing the glycine (G) at amino acid position 4969 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Ambry Genetics	RCV004460873	SCV004957997	uncertain significance	not specified	2022-03-29	criteria provided, single submitter	clinical testing	The c.15100C>T (p.P5034S) alteration is located in exon 100 (coding exon 100) of the SSPO gene. This alteration results from a C to T substitution at nucleotide position 15100, causing the proline (P) at amino acid position 5034 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Ambry Genetics	RCV004460874	SCV004957998	uncertain significance	not specified	2021-07-14	criteria provided, single submitter	clinical testing	The c.15368C>T (p.T5123I) alteration is located in exon 102 (coding exon 102) of the SSPO gene. This alteration results from a C to T substitution at nucleotide position 15368, causing the threonine (T) at amino acid position 5123 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Clinical Genetics and Genomics, Karolinska University Hospital	RCV004515750	SCV005013301	pathogenic	alpha Thalassemia	2024-03-22	criteria provided, single submitter	clinical testing
PROSPAX: an integrated multimodal progression chart in spastic ataxias, Center for Neurology; Hertie-Institute for Clinical Brain Research	RCV004765021	SCV005044514	pathogenic	Charlevoix-Saguenay spastic ataxia	2022-01-01	criteria provided, single submitter	research
PROSPAX: an integrated multimodal progression chart in spastic ataxias, Center for Neurology; Hertie-Institute for Clinical Brain Research	RCV004765037	SCV005044548	pathogenic	Hereditary spastic paraplegia 7	2022-01-01	criteria provided, single submitter	research
PROSPAX: an integrated multimodal progression chart in spastic ataxias, Center for Neurology; Hertie-Institute for Clinical Brain Research	RCV004765043	SCV005044563	pathogenic	Hereditary spastic paraplegia 7	2022-01-01	criteria provided, single submitter	research
PROSPAX: an integrated multimodal progression chart in spastic ataxias, Center for Neurology; Hertie-Institute for Clinical Brain Research	RCV004765056	SCV005044600	pathogenic	Charlevoix-Saguenay spastic ataxia	2022-01-01	criteria provided, single submitter	research
PROSPAX: an integrated multimodal progression chart in spastic ataxias, Center for Neurology; Hertie-Institute for Clinical Brain Research	RCV004765063	SCV005044618	pathogenic	Hereditary spastic paraplegia 7	2022-01-01	criteria provided, single submitter	research
PROSPAX: an integrated multimodal progression chart in spastic ataxias, Center for Neurology; Hertie-Institute for Clinical Brain Research	RCV004765075	SCV005044648	pathogenic	Hereditary spastic paraplegia 7	2022-01-01	criteria provided, single submitter	research
Cancer Genomics Group, Japanese Foundation For Cancer Research	RCV004794683	SCV005045655	likely pathogenic	Hereditary breast ovarian cancer syndrome	2023-03-27	criteria provided, single submitter	research
Cancer Genomics Group, Japanese Foundation For Cancer Research	RCV004794684	SCV005045656	likely pathogenic	Hereditary breast ovarian cancer syndrome	2023-03-27	criteria provided, single submitter	research
Ege University Pediatric Genetics, Ege University	RCV004577978	SCV005061998	likely pathogenic	Kabuki syndrome 1	2024-06-22	criteria provided, single submitter	clinical testing
Ege University Pediatric Genetics, Ege University	RCV004577979	SCV005061999	likely pathogenic	Hereditary spastic paraplegia 15	2024-06-22	criteria provided, single submitter	clinical testing
Ege University Pediatric Genetics, Ege University	RCV004577980	SCV005062000	likely pathogenic	Pyruvate dehydrogenase E3-binding protein deficiency	2024-06-22	criteria provided, single submitter	clinical testing
Ege University Pediatric Genetics, Ege University	RCV004577981	SCV005062001	pathogenic	Faundes-Banka syndrome	2024-06-22	criteria provided, single submitter	clinical testing
Ege University Pediatric Genetics, Ege University	RCV004577982	SCV005062002	pathogenic	Spastic paraplegia 52, autosomal recessive	2024-06-22	criteria provided, single submitter	clinical testing
Ege University Pediatric Genetics, Ege University	RCV004577983	SCV005062003	pathogenic	Danon disease	2024-06-22	criteria provided, single submitter	clinical testing
Ege University Pediatric Genetics, Ege University	RCV004577984	SCV005062004	pathogenic	Bardet-Biedl syndrome 9	2024-06-22	criteria provided, single submitter	clinical testing
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV004597218	SCV005088586	pathogenic	Developmental and epileptic encephalopathy, 25		criteria provided, single submitter	clinical testing
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV004597232	SCV005088608	pathogenic	Intellectual disability, autosomal dominant 20		criteria provided, single submitter	clinical testing	The 5q14.3 microdeletion syndrome encompassing the MEF2C gene has been reported in individuals with severe intellectual disability with stereotypic movements, epilepsy and/or cerebral malformations earlier (Le Meur et al. 2010).
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV004699150	SCV005201008	pathogenic	Intellectual developmental disorder with speech delay, autism, and dysmorphic facies		criteria provided, single submitter	clinical testing	Monoallelic disease-causing variants in CNOT3 are known to cause intellectual developmental disorder with speech delay, autism, and dysmorphic facies (MIM #618672). The clinical features observed in the proband overlap with intellectual developmental disorder with speech delay, autism, and dysmorphic facies.
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV004701251	SCV005201115	pathogenic	Nephronophthisis 1		criteria provided, single submitter	clinical testing	Overlapping regions with this CNV encompassing NPHP1 have also been reported in the ClinVar (ClinVar ID: 237627) database. In a study by Stokman et al. 2018, a homozygous deletion of the NPHP1 gene was reported in an affected individual with a similar phenotype. Bi-allelic variants in NPHP1 are known to cause Nephronophthisis 1, juvenile (MIM# 256100).
Breakthrough Genomics, Breakthrough Genomics	RCV004703368	SCV005218130	likely benign	not provided		criteria provided, single submitter	not provided
CeGaT Center for Human Genetics Tuebingen	RCV004722568	SCV005331002	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	ANXA8L2: PP2, BP4, BS2
Henan Neurodevelopment Engineering Research Center for Children, Children's Hospital Affiliated to Zhengzhou University	RCV004765448	SCV005374705	pathogenic	X-linked ichthyosis with steryl-sulfatase deficiency		criteria provided, single submitter	clinical testing
GeneReviews	RCV000714981	SCV000040787	pathologic	Dentatorubral-pallidoluysian atrophy	2010-06-01	no assertion criteria provided	curation	Converted during submission to Pathogenic.
GeneReviews	RCV000055842	SCV000086834	pathologic	Steinert myotonic dystrophy syndrome	2013-05-16	no assertion criteria provided	curation	Converted during submission to Pathogenic.
GeneReviews	RCV000056183	SCV000087272	pathologic	Central core myopathy	2010-05-11	no assertion criteria provided	curation	Converted during submission to Pathogenic.
GeneReviews	RCV000056189	SCV000087278	pathologic	Central core myopathy	2010-05-11	no assertion criteria provided	curation	Converted during submission to Pathogenic.
GeneReviews	RCV000056191	SCV000087280	pathologic	Central core myopathy	2010-05-11	no assertion criteria provided	curation	Converted during submission to Pathogenic.
GeneReviews	RCV000056196	SCV000087285	pathologic	Central core myopathy	2010-05-11	no assertion criteria provided	curation	Converted during submission to Pathogenic.
GeneReviews	RCV000056217	SCV000087306	pathologic	Central core myopathy	2010-05-11	no assertion criteria provided	curation	Converted during submission to Pathogenic.
GeneReviews	RCV000056219	SCV000087308	pathologic	Central core myopathy	2010-05-11	no assertion criteria provided	curation	Converted during submission to Pathogenic.
GeneReviews	RCV000056220	SCV000087309	pathologic	Central core myopathy	2010-05-11	no assertion criteria provided	curation	Converted during submission to Pathogenic.
GeneReviews	RCV000056221	SCV000087310	pathologic	Central core myopathy	2010-05-11	no assertion criteria provided	curation	Converted during submission to Pathogenic.
GeneReviews	RCV000056222	SCV000087311	pathologic	Central core myopathy	2010-05-11	no assertion criteria provided	curation	Converted during submission to Pathogenic.
GeneReviews	RCV000056225	SCV000087314	pathologic	Central core myopathy	2010-05-11	no assertion criteria provided	curation	Converted during submission to Pathogenic.
GeneReviews	RCV000056247	SCV000087336	pathologic	Central core myopathy	2010-05-11	no assertion criteria provided	curation	Converted during submission to Pathogenic.
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111479	SCV000143921	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	1997-09-04	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111480	SCV000143922	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	1999-06-21	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111482	SCV000143924	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2013-05-21	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111483	SCV000143925	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2003-11-25	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111484	SCV000143926	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2013-05-21	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111485	SCV000143927	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	2000-01-01	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111486	SCV000143928	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1	1997-09-04	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111487	SCV000143929	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 1		no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA1)	RCV000111491	SCV000143933	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2002-05-29	no assertion criteria provided	clinical testing
GeneReviews	RCV000114344	SCV000147920	pathogenic	Aicardi-Goutieres syndrome 5	2014-03-13	no assertion criteria provided	literature only
Center for Medical Genetics Ghent, University of Ghent	RCV000240951	SCV000165997	likely pathogenic	Seizure; Intellectual disability		no assertion criteria provided	case-control
Center for Medical Genetics Ghent, University of Ghent	RCV000240885	SCV000165998	likely pathogenic	Seizure; Intellectual disability		no assertion criteria provided	case-control
University of British Columbia	RCV000148350	SCV000172278	likely pathogenic	Adams-Oliver syndrome 5	2014-07-01	no assertion criteria provided	research
Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo	RCV000208718	SCV000172698	pathogenic	Autism spectrum disorder; Epilepsy	2011-08-12	no assertion criteria provided	research
Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo	RCV000208731	SCV000172699	pathogenic	Autism spectrum disorder	2011-08-12	no assertion criteria provided	research
Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo	RCV000208741	SCV000172700	pathogenic	Autism spectrum disorder; Epilepsy	2011-08-12	no assertion criteria provided	research
Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences, University of São Paulo	RCV000208724	SCV000172701	uncertain significance	Autism spectrum disorder; Epilepsy	2011-08-12	no assertion criteria provided	research
Dept. of Medical Genetics, Telemark Hospital Trust, Telemark Hospital Trust	RCV000170334	SCV000189426	uncertain significance	Charcot-Marie-Tooth disease	2014-10-01	no assertion criteria provided	research
Dept. of Medical Genetics, Telemark Hospital Trust, Telemark Hospital Trust	RCV000170335	SCV000189427	likely pathogenic	Charcot-Marie-Tooth disease	2014-10-01	no assertion criteria provided	research
Dept. of Medical Genetics, Telemark Hospital Trust, Telemark Hospital Trust	RCV000170336	SCV000189428	uncertain significance	Charcot-Marie-Tooth disease	2014-10-01	no assertion criteria provided	research
Institute of Molecular and Cell Biology, University of Tartu	RCV000161147	SCV000191104	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161148	SCV000191105	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161155	SCV000191112	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161156	SCV000191113	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161157	SCV000191114	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161158	SCV000191115	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161159	SCV000191116	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161163	SCV000191120	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161166	SCV000191123	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161169	SCV000191126	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161170	SCV000191127	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161171	SCV000191128	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161172	SCV000191129	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161173	SCV000191130	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161174	SCV000191131	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161176	SCV000191133	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161178	SCV000191135	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161179	SCV000191136	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161180	SCV000191137	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161181	SCV000191138	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161182	SCV000191139	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161183	SCV000191140	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161184	SCV000191141	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161185	SCV000191142	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161187	SCV000191144	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161188	SCV000191145	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161189	SCV000191146	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161190	SCV000191147	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161192	SCV000191149	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161193	SCV000191150	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161197	SCV000191154	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161199	SCV000191156	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161200	SCV000191157	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161202	SCV000191159	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161204	SCV000191161	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161207	SCV000191164	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161208	SCV000191165	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161212	SCV000191169	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161222	SCV000191179	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161223	SCV000191180	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161224	SCV000191181	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161225	SCV000191182	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161232	SCV000191189	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161238	SCV000191195	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161240	SCV000191197	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161241	SCV000191198	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161248	SCV000191205	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161249	SCV000191206	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161255	SCV000191212	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161256	SCV000191213	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161261	SCV000191218	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161262	SCV000191219	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161267	SCV000191224	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161281	SCV000191238	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161282	SCV000191239	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161283	SCV000191240	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161284	SCV000191241	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161285	SCV000191242	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161286	SCV000191243	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161287	SCV000191244	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161288	SCV000191245	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161289	SCV000191246	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161290	SCV000191247	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161291	SCV000191248	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161292	SCV000191249	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161294	SCV000191251	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161298	SCV000191255	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161300	SCV000191257	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161301	SCV000191258	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161302	SCV000191259	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161312	SCV000191269	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161313	SCV000191270	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161314	SCV000191271	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161315	SCV000191272	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161316	SCV000191273	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161319	SCV000191276	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161327	SCV000191284	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161328	SCV000191285	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161331	SCV000191288	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161332	SCV000191289	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161335	SCV000191292	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161336	SCV000191293	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161340	SCV000191297	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161343	SCV000191300	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161344	SCV000191301	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161345	SCV000191302	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161346	SCV000191303	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161349	SCV000191306	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161352	SCV000191309	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161353	SCV000191310	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161354	SCV000191311	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161356	SCV000191313	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161360	SCV000191317	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161362	SCV000191319	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161372	SCV000191329	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161373	SCV000191330	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161374	SCV000191331	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161375	SCV000191332	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161376	SCV000191333	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161377	SCV000191334	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161378	SCV000191335	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161379	SCV000191336	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161380	SCV000191337	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161381	SCV000191338	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161382	SCV000191339	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161383	SCV000191340	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161384	SCV000191341	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161385	SCV000191342	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161386	SCV000191343	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161387	SCV000191344	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161388	SCV000191345	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161389	SCV000191346	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161390	SCV000191347	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161391	SCV000191348	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161392	SCV000191349	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161393	SCV000191350	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161394	SCV000191351	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161404	SCV000191361	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161405	SCV000191362	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161406	SCV000191363	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161407	SCV000191364	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161409	SCV000191366	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161410	SCV000191367	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161411	SCV000191368	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161413	SCV000191370	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161414	SCV000191371	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161415	SCV000191372	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161416	SCV000191373	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161417	SCV000191374	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161418	SCV000191375	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161419	SCV000191376	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161420	SCV000191377	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161435	SCV000191392	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161436	SCV000191393	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161437	SCV000191394	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161438	SCV000191395	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161439	SCV000191396	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161442	SCV000191399	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161443	SCV000191400	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161444	SCV000191401	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161445	SCV000191402	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161446	SCV000191403	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161449	SCV000191406	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161454	SCV000191411	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161462	SCV000191419	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161464	SCV000191421	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161465	SCV000191422	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161467	SCV000191424	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161468	SCV000191425	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161474	SCV000191431	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161475	SCV000191432	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161476	SCV000191433	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161477	SCV000191434	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161478	SCV000191435	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161480	SCV000191437	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161481	SCV000191438	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161482	SCV000191439	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161484	SCV000191441	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161489	SCV000191446	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161496	SCV000191453	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161498	SCV000191455	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161499	SCV000191456	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161500	SCV000191457	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161502	SCV000191459	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161503	SCV000191460	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161509	SCV000191466	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161510	SCV000191467	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161512	SCV000191469	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161527	SCV000191484	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161528	SCV000191485	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161538	SCV000191495	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161539	SCV000191496	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161543	SCV000191500	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161544	SCV000191501	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161546	SCV000191503	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161547	SCV000191504	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161548	SCV000191505	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161549	SCV000191506	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161550	SCV000191507	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161551	SCV000191508	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161553	SCV000191510	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161559	SCV000191516	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161562	SCV000191519	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161563	SCV000191520	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161564	SCV000191521	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161565	SCV000191522	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161566	SCV000191523	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161567	SCV000191524	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161568	SCV000191525	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161569	SCV000191526	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161571	SCV000191528	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161581	SCV000191538	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161582	SCV000191539	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161584	SCV000191541	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161586	SCV000191543	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161587	SCV000191544	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161588	SCV000191545	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161589	SCV000191546	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161590	SCV000191547	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161591	SCV000191548	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161593	SCV000191550	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161594	SCV000191551	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161595	SCV000191552	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161598	SCV000191555	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161601	SCV000191558	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161602	SCV000191559	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161603	SCV000191560	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161604	SCV000191561	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161605	SCV000191562	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161609	SCV000191566	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161610	SCV000191567	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161611	SCV000191568	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161612	SCV000191569	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161614	SCV000191571	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161630	SCV000191587	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161634	SCV000191591	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161635	SCV000191592	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161636	SCV000191593	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161637	SCV000191594	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161638	SCV000191595	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161639	SCV000191596	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161640	SCV000191597	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161641	SCV000191598	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161653	SCV000191610	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161654	SCV000191611	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161655	SCV000191612	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161656	SCV000191613	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161667	SCV000191624	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161668	SCV000191625	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161684	SCV000191641	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161692	SCV000191649	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161701	SCV000191658	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161702	SCV000191659	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161703	SCV000191660	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161704	SCV000191661	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161705	SCV000191662	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161706	SCV000191663	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161707	SCV000191664	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161709	SCV000191666	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161710	SCV000191667	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161714	SCV000191671	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161715	SCV000191672	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161717	SCV000191674	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161724	SCV000191681	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161725	SCV000191682	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161726	SCV000191683	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161727	SCV000191684	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161728	SCV000191685	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161731	SCV000191688	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161733	SCV000191690	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161736	SCV000191693	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161737	SCV000191694	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161738	SCV000191695	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161739	SCV000191696	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161740	SCV000191697	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161741	SCV000191698	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161742	SCV000191699	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161743	SCV000191700	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161744	SCV000191701	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161750	SCV000191707	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161751	SCV000191708	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161752	SCV000191709	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161753	SCV000191710	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161764	SCV000191721	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161768	SCV000191725	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161770	SCV000191727	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161772	SCV000191729	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161773	SCV000191730	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161774	SCV000191731	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161779	SCV000191736	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161781	SCV000191738	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161782	SCV000191739	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161784	SCV000191741	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161785	SCV000191742	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161786	SCV000191743	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161790	SCV000191747	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161791	SCV000191748	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161793	SCV000191750	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161795	SCV000191752	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161796	SCV000191753	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161798	SCV000191755	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161800	SCV000191757	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161801	SCV000191758	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161802	SCV000191759	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161803	SCV000191760	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161810	SCV000191767	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161822	SCV000191779	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161823	SCV000191780	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161824	SCV000191781	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161825	SCV000191782	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161826	SCV000191783	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161828	SCV000191785	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161833	SCV000191790	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161834	SCV000191791	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161835	SCV000191792	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161841	SCV000191798	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161853	SCV000191810	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161854	SCV000191811	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161855	SCV000191812	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161856	SCV000191813	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161857	SCV000191814	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161858	SCV000191815	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161859	SCV000191816	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161860	SCV000191817	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161861	SCV000191818	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161862	SCV000191819	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161863	SCV000191820	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161864	SCV000191821	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161865	SCV000191822	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161872	SCV000191829	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161873	SCV000191830	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161874	SCV000191831	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161875	SCV000191832	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161876	SCV000191833	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161877	SCV000191834	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161878	SCV000191835	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161879	SCV000191836	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161880	SCV000191837	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161881	SCV000191838	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161883	SCV000191840	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161886	SCV000191843	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161889	SCV000191846	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161890	SCV000191847	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161891	SCV000191848	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161893	SCV000191850	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161899	SCV000191856	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161900	SCV000191857	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161901	SCV000191858	not provided	Gestational diabetes mellitus uncontrolled		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161902	SCV000191859	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161903	SCV000191860	not provided	Small for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161904	SCV000191861	not provided	Large for gestational age		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161905	SCV000191862	not provided	Preeclampsia		no assertion provided	case-control
Institute of Molecular and Cell Biology, University of Tartu	RCV000161907	SCV000191864	not provided	Normal pregnancy		no assertion provided	case-control
Institute of Pediatric Research, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine	RCV000162212	SCV000212221	pathogenic	Multiple congenital anomalies/dysmorphic syndrome-intellectual disability	2015-03-02	no assertion criteria provided	clinical testing
Vavilov Institute of General Genetics RAS, Laboratory of Evolutional Genomics	RCV000190540	SCV000221290	protective	Spinocerebellar ataxia, X-linked		no assertion criteria provided	case-control
Lyon Laboratory, Cold Spring Harbor Laboratory	RCV000186553	SCV000239874	uncertain significance	Autism	2015-07-21	no assertion criteria provided	research
Lyon Laboratory, Cold Spring Harbor Laboratory	RCV000186554	SCV000239875	uncertain significance	Autism	2015-07-21	no assertion criteria provided	research
Lyon Laboratory, Cold Spring Harbor Laboratory	RCV000186555	SCV000239876	uncertain significance	Autism	2015-07-21	no assertion criteria provided	research
GeneReviews	RCV000192286	SCV000243795	pathogenic	Dent disease type 1	2014-09-25	no assertion criteria provided	literature only
GeneReviews	RCV000192287	SCV000243796	pathogenic	Hypophosphatemic rickets, X-linked recessive	2014-09-25	no assertion criteria provided	literature only
GeneReviews	RCV000192288	SCV000243799	pathogenic	Lowe syndrome	2014-09-25	no assertion criteria provided	literature only
GeneReviews	RCV000192292	SCV000243803	pathogenic	Dent disease type 2	2014-09-25	no assertion criteria provided	literature only
Science and Research Branch, Islamic Azad University, Islamic Azad University	RCV000234789	SCV000245345	pathogenic	Tyrosinase-positive oculocutaneous albinism	2015-08-01	no assertion criteria provided	clinical testing
GeneReviews	RCV000191989	SCV000246252	pathogenic	Maternal riboflavin deficiency	2015-03-17	no assertion criteria provided	literature only
Next Generation Diagnostics, Novartis Institutes for BioMedical Research, Inc.	RCV000207058	SCV000258684	uncertain significance	Breast ductal adenocarcinoma	2015-07-20	no assertion criteria provided	research
Next Generation Diagnostics, Novartis Institutes for BioMedical Research, Inc.	RCV000207145	SCV000258685	uncertain significance	Breast ductal adenocarcinoma	2015-07-20	no assertion criteria provided	research
Next Generation Diagnostics, Novartis Institutes for BioMedical Research, Inc.	RCV000207271	SCV000258686	uncertain significance	Breast ductal adenocarcinoma	2015-07-20	no assertion criteria provided	research
Next Generation Diagnostics, Novartis Institutes for BioMedical Research, Inc.	RCV000207086	SCV000258687	uncertain significance	Breast ductal adenocarcinoma	2015-07-20	no assertion criteria provided	research
Next Generation Diagnostics, Novartis Institutes for BioMedical Research, Inc.	RCV000207259	SCV000258689	uncertain significance	Breast ductal adenocarcinoma	2015-07-20	no assertion criteria provided	research
Next Generation Diagnostics, Novartis Institutes for BioMedical Research, Inc.	RCV000207075	SCV000258690	uncertain significance	Breast ductal adenocarcinoma	2015-07-20	no assertion criteria provided	research
Next Generation Diagnostics, Novartis Institutes for BioMedical Research, Inc.	RCV000207202	SCV000258691	uncertain significance	Breast ductal adenocarcinoma	2015-07-20	no assertion criteria provided	research
Next Generation Diagnostics, Novartis Institutes for BioMedical Research, Inc.	RCV000207325	SCV000258692	uncertain significance	Breast ductal adenocarcinoma	2015-07-20	no assertion criteria provided	research
Next Generation Diagnostics, Novartis Institutes for BioMedical Research, Inc.	RCV000207104	SCV000258693	uncertain significance	Breast ductal adenocarcinoma	2015-07-20	no assertion criteria provided	research
Next Generation Diagnostics, Novartis Institutes for BioMedical Research, Inc.	RCV000207314	SCV000258695	uncertain significance	Breast ductal adenocarcinoma	2015-07-20	no assertion criteria provided	research
Next Generation Diagnostics, Novartis Institutes for BioMedical Research, Inc.	RCV000207129	SCV000258696	uncertain significance	Breast ductal adenocarcinoma	2015-07-20	no assertion criteria provided	research
Next Generation Diagnostics, Novartis Institutes for BioMedical Research, Inc.	RCV000207027	SCV000258698	uncertain significance	Breast ductal adenocarcinoma	2015-07-20	no assertion criteria provided	research
Next Generation Diagnostics, Novartis Institutes for BioMedical Research, Inc.	RCV000207119	SCV000258699	uncertain significance	Breast ductal adenocarcinoma	2015-07-20	no assertion criteria provided	research
GeneReviews	RCV000208785	SCV000264778	pathogenic	Chromosome 17q12 duplication syndrome	2015-12-16	no assertion criteria provided	literature only
Centre of Medical Genetics, University of Antwerp	RCV000256227	SCV000266571	pathogenic	Familial thoracic aortic aneurysm and aortic dissection		no assertion criteria provided	research
Department of Medical Biochemistry and Genetics, University of Turku	RCV000258007	SCV000281776	likely pathogenic	Idiopathic basal ganglia calcification 1		no assertion criteria provided	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000491645	SCV000282199	pathogenic	Autosomal recessive spinocerebellar ataxia 18	2016-01-10	no assertion criteria provided	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000491504	SCV000282213	likely pathogenic	Global developmental delay; Hypoplasia of the corpus callosum; Abnormal cerebral white matter morphology; Periventricular leukomalacia; Delayed myelination; Hypotonia	2016-01-10	no assertion criteria provided	research
GeneReviews	RCV000225363	SCV000282239	pathogenic	15q11q13 microduplication syndrome	2016-03-02	no assertion criteria provided	literature only
GeneReviews	RCV000239455	SCV000297825	pathogenic	Autosomal recessive nonsyndromic hearing loss 1A	2016-08-18	no assertion criteria provided	literature only
Zuffardi lab, University of Pavia	RCV000258283	SCV000328241	pathogenic	16q24.3 microdeletion syndrome	2016-08-01	no assertion criteria provided	clinical testing
Zuffardi lab, University of Pavia	RCV000258380	SCV000328242	pathogenic	16q24.3 microdeletion syndrome	2016-08-01	no assertion criteria provided	clinical testing
Zuffardi lab, University of Pavia	RCV000258180	SCV000328243	pathogenic	16q24.3 microdeletion syndrome	2016-08-01	no assertion criteria provided	clinical testing
Zuffardi lab, University of Pavia	RCV000258300	SCV000328244	pathogenic	16q24.3 microdeletion syndrome	2016-08-01	no assertion criteria provided	clinical testing
Zuffardi lab, University of Pavia	RCV000258442	SCV000328245	pathogenic	16q24.3 microdeletion syndrome	2016-08-01	no assertion criteria provided	clinical testing
Zuffardi lab, University of Pavia	RCV000258213	SCV000328246	pathogenic	16q24.3 microdeletion syndrome	2016-08-01	no assertion criteria provided	clinical testing
Zuffardi lab, University of Pavia	RCV000258311	SCV000328247	pathogenic	16q24.3 microdeletion syndrome	2016-08-01	no assertion criteria provided	clinical testing
Zuffardi lab, University of Pavia	RCV000258457	SCV000328248	pathogenic	16q24.3 microdeletion syndrome	2016-08-01	no assertion criteria provided	clinical testing
Zuffardi lab, University of Pavia	RCV000258230	SCV000328249	pathogenic	16q24.3 microdeletion syndrome	2016-08-01	no assertion criteria provided	clinical testing
Zuffardi lab, University of Pavia	RCV000258358	SCV000328250	pathogenic	16q24.3 microdeletion syndrome	2016-08-01	no assertion criteria provided	clinical testing
Zuffardi lab, University of Pavia	RCV000258474	SCV000328251	pathogenic	16q24.3 microdeletion syndrome	2016-08-01	no assertion criteria provided	clinical testing
Zuffardi lab, University of Pavia	RCV000258201	SCV000328252	pathogenic	16q24.3 microdeletion syndrome	2016-08-01	no assertion criteria provided	clinical testing
Department Of Pediatrics And Neonatology, Nagoya City University Graduate School Of Medical Sciences	RCV000496984	SCV000328419	pathogenic	Vici syndrome	2016-08-11	no assertion criteria provided	research	Patient, a 2 year-old girl, showed severe developmental delay,hypotonia, hypopigmentation, and high-arched palate. Her last head circumference was 42.5 (-3.4SD). This mutation was confirmed compound geterozygosity.
Pediatric Highly Intensive Care Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	RCV000258876	SCV000328420	pathogenic	16p13.2-p13.13 microduplication syndrome	2016-05-01	no assertion criteria provided	clinical testing
Baylor Genetics	RCV000414986	SCV000328750	pathogenic	Chromosome 1q21.1 deletion syndrome		no assertion criteria provided	clinical testing	Our laboratory reported two molecular diagnoses, a variant in CTNNB1 (NM_001904.3, c.283C>T) and a 1q21.1q21.2 deletion, in an individual with global developmental delay, intellectual disability, hypotonia, hypertonia/spasticity, dysmorphic features, microcephaly, hyperextensibility, joint contractures and failure to thrive.
Baylor Genetics	RCV000414764	SCV000328752	likely pathogenic	Global developmental delay; Seizure; Intellectual disability		no assertion criteria provided	clinical testing	Our laboratory reported two molecular diagnoses, a variant in SOX11 (NM_003108.3:c.1286G>A) and a 17q11.2 duplication, in an individual with delayed motor milestones, delayed speech, intellectual disability, autism, attention deficit hyperactivity disorder, aggression, oppositional defiant disorder, episodes of staring spells, and mild dysmorphic features (incomplete synophrys and short pedal digits).
Baylor Genetics	RCV000414871	SCV000328812	pathogenic	Becker muscular dystrophy; Duchenne muscular dystrophy	2015-09-05	no assertion criteria provided	clinical testing	Our laboratory reported dual molecular diagnoses in KIF5C (NM_004522.2, c.709G>A) and DMD (exon 49 deletion) in this individual reported to have features of global developmental delay, seizures, abnormal tooth eruption, autism, cortical brain dysplasia, aggressive behavior, balance abnormalities, and strabismus.
Baylor Genetics	RCV000414802	SCV000328842	pathogenic	Infantile neuroaxonal dystrophy	2015-12-07	no assertion criteria provided	clinical testing	Our laboratory reported dual molecular diagnoses in PLA2G6 (homozygous exon 2 deletion) and BCAP31 (NM_001139457.2, c.107C>A) in one individual with reported features which included delayed motor milestones, developmental regression, dysphagia, central hypotonia, vision loss, esotropia, cryptorchidism, cerebellar atrophy with a flattened pons and hypoplasia of the inferior vermis.
Baylor Genetics	RCV000415202	SCV000328856	pathogenic	Becker muscular dystrophy; Duchenne muscular dystrophy	2015-09-05	no assertion criteria provided	clinical testing	Our laboratory reported dual molecular diagnoses in SMC1A (NM_006306.3, c.586C>T) and DMD (exon 49-51 deletion) in one individual with reported features of profound motor delay, bilateral hearing loss, diffused hypotonia, dysmorphia, cleft palate, microcephaly, vision loss, congenital heart disease.
GeneReviews	RCV000412525	SCV000490151	pathogenic	Hypercholesterolemia, familial, 1	2016-12-08	no assertion criteria provided	literature only
GeneReviews	RCV000412586	SCV000490152	pathogenic	Hypercholesterolemia, familial, 1	2016-12-08	no assertion criteria provided	literature only
GeneReviews	RCV000417218	SCV000503062	pathogenic	alpha Thalassemia	2016-12-29	no assertion criteria provided	literature only
Medical Genetics Laboratory, Aldo Moro University of Bari	RCV000509569	SCV000537200	pathogenic	Chromosome 10q23 deletion syndrome	2016-12-21	no assertion criteria provided	clinical testing	First case of multiple autoimmune disorders, associated with Juvenile Polyposis and epilepsy, in a patient with a de novo heterozygous germline 10q23.1-q23.31 deletion. This deletion disrupts GRID1 and RNLS (on breakpoints), and involves 32 annotated genes and transcripts, seven of which (i.e. PTEN, BMPR1A, LDB3, GLUD1, MIMPP1, PAPSS2 and KLLN) are associated with human diseases. Patients with JP due to 10q23 deletions appear at increased risk of developing not only thyroid, but also gastrointestinal autoimmune disorders, an aspect that has to be carefully considered in the multidisciplinary patient management, for the associated systemic short- and long-term health consequences.
Department of Medical Sciences, Uppsala University	RCV000490683	SCV000574670	pathogenic	Osteogenesis imperfecta type I		no assertion criteria provided	clinical testing
Department of Obstetrics and Gynecology, Helsinki University Hospital	RCV000515705	SCV000576419	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 3	2017-05-01	no assertion criteria provided	research
Flegel Lab, National Institutes of Health	RCV000495883	SCV000583609	pathogenic	RHD DEL	2017-05-30	no assertion criteria provided	clinical testing
Flegel Lab, National Institutes of Health	RCV000495911	SCV000583610	pathogenic	RHD DEL	2017-05-30	no assertion criteria provided	clinical testing
Baylor Genetics	RCV000577928	SCV000584203	pathogenic	Global developmental delay; Expressive language delay; Secondary microcephaly	2017-07-03	no assertion criteria provided	clinical testing	This deletion involving BPTF and 2 additional genes was observed once in our laboratory de novo in a 10-year-old female with intellectual disability, hypotonia, postnatal microcephaly, mild dysmorphisms, advanced bone age.
Baylor Genetics	RCV000577886	SCV000584204	pathogenic	Global developmental delay; Expressive language delay; Secondary microcephaly	2017-07-03	no assertion criteria provided	clinical testing	This deletion involving BPTF alone was observed once in our laboratory (inheritance unknown) in a 4-year-old female with short stature, autistic features, speech delay, microcephaly, dysmorphic features, failure to thrive.
Laboratory of Genetics, AOUP, Azienda Ospedaliera Universitaria Pisana	RCV000503510	SCV000590913	pathogenic	Blepharophimosis, ptosis, and epicanthus inversus syndrome	2017-08-22	no assertion criteria provided	clinical testing	The deletion is 278 kb uspstream of FOXL2, and affects the regulatory elements of this gene, causing BPES and additional clinical signs like microcephaly.
Biologia e Medicina Molecolare, Sapienza University of Rome	RCV000505090	SCV000598565	pathogenic	Cleidocranial dysostosis	2016-08-31	no assertion criteria provided	clinical testing	Abnormalities in the bones and teeth
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504681	SCV000599201	likely pathogenic	Severe early-childhood-onset retinal dystrophy		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504694	SCV000599204	likely pathogenic	Cone dystrophy		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504885	SCV000599205	likely pathogenic	Retinitis pigmentosa		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504706	SCV000599207	likely pathogenic	Retinitis pigmentosa		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504897	SCV000599208	likely pathogenic	Retinitis pigmentosa		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504728	SCV000599210	likely pathogenic	Retinitis pigmentosa		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000505177	SCV000599212	likely pathogenic	Retinitis pigmentosa		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504805	SCV000599213	likely pathogenic	Retinitis pigmentosa		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000505115	SCV000599215	likely pathogenic	Retinitis pigmentosa		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000505010	SCV000599217	likely pathogenic	Cone dystrophy		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504833	SCV000599219	likely pathogenic	Usher syndrome		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504658	SCV000599221	likely pathogenic	Retinitis pigmentosa		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000505035	SCV000599223	likely pathogenic	Retinal dystrophy		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000505056	SCV000599226	likely pathogenic	Retinitis pigmentosa		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000505140	SCV000599229	likely pathogenic	Retinitis pigmentosa		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000505151	SCV000599232	likely pathogenic	Usher syndrome		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV000504785	SCV000599233	likely pathogenic	Retinitis pigmentosa		no assertion criteria provided	research
GenomeConnect, ClinGen	RCV000509506	SCV000607109	not provided	Intellectual disability-hypotonic facies syndrome, X-linked, 1		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Molecular Genetics Laboratory, Institute for Ophthalmic Research	RCV000656139	SCV000612182	pathogenic	Cone monochromatism	2017-11-21	no assertion criteria provided	research	De novo mutation
Undiagnosed Diseases Network, NIH	RCV000529276	SCV000622159	pathogenic	Nephronophthisis 1; Senior-loken syndrome 3	2016-06-20	no assertion criteria provided	clinical testing	Pathogenic homozygous deletion based on previous publications
Prof. Thelma's Laboratory, Department of Genetics, University of Delhi South Campus	RCV000684766	SCV000681417	likely pathogenic	Intellectual disability		no assertion criteria provided	research	The de novo deletion at 13q14.2-q21.1 is observed in two siblings with mid Intellectual disability. Other clinical features observed include large face, Large ears, short philtrum, congenital cataract, disproportionate body (LS>US), body skeletal development poor, thinness in rib cage, short stature, impaired cognition, IQ is low, unclear speech, hyperactivity, depression, joint hyperlaxicity/hypotonia, arachnodactyly (spider fingers), prognathism, teeth and gum problems. The deleted region encompasses functionally relevant genes and therefore the haploinsufficiency of the respective genes may contribute to disease phenotype.
Genome Sciences Centre, British Columbia Cancer Agency	RCV000585807	SCV000693715	likely pathogenic	Pediatric metastatic thyroid tumour	2018-01-19	no assertion criteria provided	research
Bioscientia Institut fuer Medizinische Diagnostik GmbH, Sonic Healthcare	RCV000625585	SCV000746084	pathogenic	Polycystic kidney disease, adult type	2017-09-18	no assertion criteria provided	clinical testing
Institute of Cellular and Molecular Medicine, Copenhagen University	RCV000714264	SCV000747864	likely pathogenic	not provided	2018-02-02	no assertion criteria provided	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000754881	SCV000778478	likely pathogenic	Primary ciliary dyskinesia 3	2018-05-28	no assertion criteria provided	research
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000754893	SCV000778491	uncertain significance	Anomalous pulmonary venous return	2018-05-28	no assertion criteria provided	research	A rare variant in SMAD2 (p.S64fs) was identified in a single proband with anomalous venous return. This gene has not been previously associated with human disease.
Laboratoire de Génétique Moléculaire, CHU Bordeaux	RCV000736029	SCV000786655	pathogenic	Polydactyly; Heart, malformation of; Bilateral cleft lip and palate; Phocomelia	2018-07-18	no assertion criteria provided	clinical testing	This de novo deletion has been observed in a fetus, and fit the disruption of TAD boundaries model studied at this locus by Lupianez et al. (Cell 2015 : Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. PMID: 25959774)
Medical Genetics Lab, Policlinico S. Orsola.Malpighi	RCV000677104	SCV000803175	uncertain significance	Ebstein anomaly; Decreased response to growth hormone stimulation test; Intellectual disability, mild	2018-05-01	no assertion criteria provided	clinical testing	This is a small, rare, de novo duplication. Three genes are involved but none is known to be relevant for neurologic development.
Medical Genetics Lab, Policlinico S. Orsola.Malpighi	RCV000677105	SCV000803176	uncertain significance	Atypical behavior; Moderate global developmental delay	2018-05-01	no assertion criteria provided	clinical testing	This is a small de novo deletion. Only the IMMP2L gene is deleted, which is a candidate for neurologic development. However, overlapping deletions are reported in databases (defined as likely benign/uncertain significance) and are often transmitted by healthy parents.
Medical Genetics Lab, Policlinico S. Orsola.Malpighi	RCV000677106	SCV000803177	uncertain significance	Autistic behavior; Absent speech	2018-05-01	no assertion criteria provided	clinical testing	This is a small de novo deletion. Only the SND1 gene is deleted, which was identified as candidate gene for autism by linkage analysis (literature). ClinVar reports a small deletion of SND1 (and the neighboring LRRC4 gene) in a patient with global developmental delay; origin is unknown.
Medical Genetics Lab, Policlinico S. Orsola.Malpighi	RCV000677108	SCV000803179	uncertain significance	Seizure; Fetal growth restriction; Narrow nasal bridge; Mandibular prognathia; Delayed speech and language development	2018-05-01	no assertion criteria provided	clinical testing	This is a small, rare, de novo duplication. ClinVar reports three similar overlapping duplications, two defined as of uncertain significance, one benign. The patient carries a second de novo duplication of uncertain significance (dup2p23.3 Chr2: 24807000 - 25700000 on GRCh37)
Medical Genetics Lab, Policlinico S. Orsola.Malpighi	RCV000677109	SCV000803180	uncertain significance	Failure to thrive in infancy; Attention deficit hyperactivity disorder	2018-05-01	no assertion criteria provided	clinical testing	This is a small de novo deletion. Only the PLXDC2 gene is deleted, which is not known to be relevant for neurologic development.
Medical Genetics Lab, Policlinico S. Orsola.Malpighi	RCV000677110	SCV000803181	uncertain significance	Global developmental delay; Seizure; Hypotelorism; Short philtrum; Infantile muscular hypotonia	2018-05-01	no assertion criteria provided	clinical testing	This is a small, rare, de novo duplication. ClinVar reports one similar overlapping duplication, defined as of uncertain significance.
Medical Genetics Lab, Policlinico S. Orsola.Malpighi	RCV000677111	SCV000803182	uncertain significance	Atypical behavior; Low-set ears; Prominent nasal bridge; Underdeveloped nasal alae; Intellectual disability, mild; Secondary microcephaly	2018-05-01	no assertion criteria provided	clinical testing	This is a small, rare, de novo deletion. Three genes are involved but none is known to be relevant for neurologic development.
Medical Genetics Lab, Policlinico S. Orsola.Malpighi	RCV000677112	SCV000803183	likely pathogenic	Isolated Pierre-Robin syndrome; Intellectual disability, mild; Bilateral conductive hearing impairment; Abnormal esophagus physiology	2018-09-26	no assertion criteria provided	clinical testing	This is a small, rare, de novo duplication. Several genes are involved. In the medical literature, a 17p13.1 microduplication syndrome has been described, based on report of six distinct patients with overlapping 17p13.1 duplications and similar clinical features. Considering the de novo origin and the clinical overlap with other patients carrying 17p13.1 duplications, we classify this CNV as likely pathogenic. The patient carries a second de novo CNV of uncertain significance (trp2q31.3 Chr2: 172,344,870 - 173,038,935 on GRCh37).
Medical Genetics Lab, Policlinico S. Orsola.Malpighi	RCV000677113	SCV000803184	likely pathogenic	Seizure	2018-05-01	no assertion criteria provided	clinical testing	This is a small, rare duplication. A brother with epilepsy carries the same CNV, but this was absent in their mother, who likely has germline mosaicism. The duplication involves seven OMIM genes, mutations in two (KIF4A and DLG3) cause intellectual disability and seizures in males. ClinVar reports a similar duplication (nsv931013) in a patient with seizures and autistic behavior, defined as of uncertain significance.
Michaelson Lab, University of Iowa	RCV000722092	SCV000853278	uncertain significance	Autism	2018-08-01	no assertion criteria provided	research
Molecular Pathology Diagnostics Labratory, University of Iowa Hospitals & Clinics	RCV000754611	SCV000864217	likely pathogenic	Renal transitional cell carcinoma	2019-01-14	no assertion criteria provided	clinical testing	This particular fusion has not been functionally characterized, however, Ross, 2016 analyzed 20,573 cases of solid tumors and detected BRAF fusions that contained the entire kinase domain in fifty-five cases. BRAF fusions were shown to be activating and oncogenic (Ross, 2016; Botton, 2013; Ciampi, 2005; Jones, 2008; Palanisamy, 2010).
Genetic Diseases Diagnostic Center, Koc University Hospital	RCV000786062	SCV000864393	likely pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2B	2018-12-18	no assertion criteria provided	clinical testing
Undiagnosed Diseases Program Translational Research Laboratory, National Institutes of Health	RCV000754630	SCV000882431	pathogenic	Kilquist syndrome	2019-01-22	no assertion criteria provided	research
Mayo Clinic Genomics Laboratory, Mayo Clinic	RCV000754715	SCV000882548	pathogenic	T-cell acute lymphoblastic leukemia	2017-08-24	no assertion criteria provided	clinical testing	Results in NUP214-ABL1 fusion, previously described in T-Acute lymphoblastic leukemia, may be responsive to tyrosine kinase inhibitors
Molecular Pathology Diagnostics Labratory, University of Iowa Hospitals & Clinics	RCV000754871	SCV000882596	likely pathogenic	Glioma	2017-06-05	no assertion criteria provided	clinical testing	FDA indication for advanced solid tumors with NTRK2 fusions.
Biochemistry Laboratory of CDMU, Chengde Medical University	RCV000768450	SCV000899213	likely pathogenic	not provided		no assertion criteria provided	case-control
Biochemistry Laboratory of CDMU, Chengde Medical University	RCV000768451	SCV000899214	likely pathogenic	not provided		no assertion criteria provided	case-control
Biochemistry Laboratory of CDMU, Chengde Medical University	RCV000768452	SCV000899215	likely pathogenic	not provided		no assertion criteria provided	case-control
Biochemistry Laboratory of CDMU, Chengde Medical University	RCV000768453	SCV000899216	likely pathogenic	not provided		no assertion criteria provided	case-control
Biochemistry Laboratory of CDMU, Chengde Medical University	RCV000768454	SCV000899217	pathogenic	Deletion of long arm of chromosome 18		no assertion criteria provided	case-control
Biochemistry Laboratory of CDMU, Chengde Medical University	RCV000768455	SCV000899218	pathogenic	Syndromic X-linked intellectual disability Lubs type		no assertion criteria provided	case-control
Biochemistry Laboratory of CDMU, Chengde Medical University	RCV000768456	SCV000899219	likely pathogenic	not provided		no assertion criteria provided	case-control
Biochemistry Laboratory of CDMU, Chengde Medical University	RCV000768457	SCV000899220	pathogenic	not provided		no assertion criteria provided	case-control
Biochemistry Laboratory of CDMU, Chengde Medical University	RCV000768458	SCV000899221	likely pathogenic	not provided		no assertion criteria provided	case-control
Biochemistry Laboratory of CDMU, Chengde Medical University	RCV000768459	SCV000899222	likely pathogenic	not provided		no assertion criteria provided	case-control
Daryl Scott Lab, Baylor College of Medicine	RCV000779600	SCV000914226	pathogenic	Aminoaciduria	2019-05-14	no assertion criteria provided	clinical testing	Aminoaciduria is seen in a 11 years old male with a hemizygous deletion involving the CLTRN gene.
Clinical Genetics Research Group, Karolinska Institutet	RCV000986105	SCV000930653	pathogenic	Esophageal atresia; Seizure; Neurodevelopmental delay; Ventricular septal defect	2019-05-01	no assertion criteria provided	research	The complex aberration detected by oligo array in DNA from esophageal tissue has varying log2-ratios. The observed log2-ratios indicate triplication for a large part of the region between the 15q segmental duplications commonly referred to as BP2 and BP3 (the triplicated region reaching as far as the GABRG3 gene), followed by duplication of the region from GABRG3 to BP4. Chromosome anlaysis performed on cultured lymphocytes from peripheral blood revealed mosaicism for different cell lines with varying rearrangements of the additional chromosomal material: 46,XX,add(15)(p10)[12]/47,XX,15ps-,+mar[8]/46,XX,15ps-[2]. FISH analysis identified the extra material on 15p as comprising an additional 15 centromere, two additional copies of proximal 15q and one additional copy of 15p. The marker chromosome had one 15 centromere, two copies of proximal 15q and one copy of 15p. The two most abundant aberrant cell lines result in the same net gain of chromosome 15q-material, equaling partial tetrasomy 15 or inv dup(15) in 20/23 cells (87%). In the two cell populations that did not carry the add(15)p rearrangement, one of the chromosome 15 homologues lacked a p-arm (15ps-). The patient phenotype is consistent with the one described for partial tetrasomy 15q, except for esophageal atresia. The complex aberration occured together with a deletion on chromosom 15 of unclear clinical significance, chr15:100923767-101626187 (hg19).
GenomeConnect, ClinGen	RCV000844896	SCV000986699	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as benign and reported on 12/30/2017 by GTR ID Perkin Elmer. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000844897	SCV000986700	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as benign and reported on 12/30/2017 by GTR ID Perkin Elmer. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000844899	SCV000986705	not provided	Tatton-Brown-Rahman overgrowth syndrome		no assertion provided	phenotyping only	Variant interpretted as pathogenic and reported on 05/10/2017 by GTR ID Lineagen, Inc. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000844900	SCV000986706	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 05/10/2017 by GTR ID Lineagen, Inc. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000844901	SCV000986707	not provided	Chromosome 1q21.1 deletion syndrome		no assertion provided	phenotyping only	Variant interpretted as pathogenic and reported on 04/12/2013 by GTR ID Integrated Genetics. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000844902	SCV000986708	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 04/12/2013 by GTR ID Integrated Genetics. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000844925	SCV000986740	not provided	Rubinstein-Taybi syndrome due to 16p13.3 microdeletion		no assertion provided	phenotyping only	Variant interpretted as pathogenic and reported on 12/04/2017 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000844927	SCV000986742	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as pathogenic and reported on 02/16/2018 by GTR ID 500068. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000844933	SCV000986749	not provided	Chromosome 2q23.1 deletion syndrome		no assertion provided	phenotyping only	Variant interpretted as pathogenic and reported on 01/12/2018 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000844956	SCV000986781	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as Likely pathogenic and reported on 02/28/2018 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000844961	SCV000986786	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as pathogenic and reported on 05/09/2018 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000844963	SCV000986788	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 02/07/2017 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000844964	SCV000986789	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 05/08/2017 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000844966	SCV000986791	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 05/25/2017 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000844974	SCV000986800	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 06/29/2018 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000844978	SCV000986804	not provided	Autosomal recessive nonsyndromic hearing loss 84B		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 06/29/2018 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000844983	SCV000986810	not provided	Lynch syndrome		no assertion provided	phenotyping only	Variant interpretted as pathogenic and reported on 07/24/2017 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000844986	SCV000986813	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 01/00/1900 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000845004	SCV000986834	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 07/24/2018 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000845021	SCV000986854	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as pathogenic and reported on 07/19/2018 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000845034	SCV000986870	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 01/31/2017 by GTR ID Lineagen, Inc. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000845038	SCV000986875	not provided	Chromosome Xp21 deletion syndrome		no assertion provided	phenotyping only	Variant interpretted as pathogenic and reported on 10/11/2018 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000845041	SCV000986878	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 10/17/2018 by GTR ID 500068. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000845075	SCV000986918	not provided	Ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome		no assertion provided	phenotyping only	Variant interpretted as not providedand reported on 08/12/2015 by GTR ID Kleberg Cytogenetics Laboratory. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000845076	SCV000986919	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as not providedand reported on 08/12/2015 by GTR ID Kleberg Cytogenetics Laboratory. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000845079	SCV000986923	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 12/03/2018 by GTR ID Lineagen, Inc. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
GenomeConnect, ClinGen	RCV000845097	SCV000986949	not provided	not provided		no assertion provided	phenotyping only	Variant interpretted as Uncertain significance and reported on 12/17/2018 by GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Daryl Scott Lab, Baylor College of Medicine	RCV000852384	SCV000992310	pathogenic	Aminoaciduria	2019-09-07	no assertion criteria provided	clinical testing	This change was seen in an individual with aminoaciduria, psychiatric/behavioral phenotypes, and an intermittent photosensitive dermatitis phenotype similar to that seen in Hartnup disease.
Genome Sciences Centre, British Columbia Cancer Agency	RCV000993802	SCV000996023	likely pathogenic	Squamous cell carcinoma of the head and neck	2019-07-19	no assertion criteria provided	research
GeneDx	RCV001004047	SCV001142746	pathogenic	not provided	2019-06-03	flagged submission	clinical testing	The c.1276_1277insAlu variant in the EFTUD2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This individual harbors a mobile insertion element that consists of Alu sequence that is approximately 300 base pairs in length and is predicted to cause loss of normal protein function. Mobile insertion elements, including retrotransposon-mediated events such as Alu inserts, are estimated to account for 1 in 600 disease causing variants (Kazazian et al., 1999). Therefore, we interpret c.1276_1277insAlu as a pathogenic variant.
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003841	SCV001162292	likely pathogenic	Gingival bleeding; Impaired epinephrine-induced platelet aggregation; Impaired collagen-induced platelet aggregation; Impaired arachidonic acid-induced platelet aggregation; Impaired ristocetin-induced platelet aggregation; Impaired thrombin-induced platelet aggregation; Impaired thromboxane A2 agonist-induced platelet aggregation		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001004037	SCV001162294	likely pathogenic	Abnormal thrombosis; Protein S deficiency disease		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001004031	SCV001162295	likely pathogenic	Hereditary factor XI deficiency disease		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003843	SCV001162296	pathogenic	Paris-Trousseau thrombocytopenia		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003853	SCV001162306	pathogenic	DiGeorge syndrome		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001004038	SCV001162310	likely pathogenic	Spastic paraplegia		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003865	SCV001162319	pathogenic	Dystonic disorder		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001004039	SCV001162320	likely pathogenic	Focal-onset seizure		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001004040	SCV001162322	pathogenic	Dystonic disorder; Global developmental delay; Ichthyosis		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003868	SCV001162324	likely pathogenic	Global developmental delay; Microcephaly; Abnormal cerebellum morphology		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001004033	SCV001162326	pathogenic	Pulmonary arterial hypertension		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001004034	SCV001162327	pathogenic	Pulmonary arterial hypertension		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001004035	SCV001162328	likely pathogenic	Pulmonary arterial hypertension		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001004036	SCV001162329	pathogenic	Pulmonary arterial hypertension		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001004041	SCV001162332	likely pathogenic	Pulmonary arterial hypertension		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003890	SCV001162351	likely pathogenic	Pulmonary arterial hypertension		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003891	SCV001162352	likely pathogenic	Pulmonary arterial hypertension		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001004032	SCV001162353	likely pathogenic	Mesangiocapillary glomerulonephritis		no assertion criteria provided	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003892	SCV001162354	likely pathogenic	Short stature; Failure to thrive; Anemia; Strabismus; Splenomegaly; Sparse hair; Neurodevelopmental delay; Thrombocytopenia		no assertion criteria provided	research
GenomeConnect-Association for Creatine Deficiencies, Association for Creatine Deficiencies	RCV001009611	SCV001169713	not provided	Creatine transporter deficiency		no assertion provided	phenotyping only	Variant interpreted as Pathogenic and reported on 06-09-2017 by GTR ID 1006. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect facilitates ClinVar submission from the Association for Creatine Deficiencies registry and does not attempt to reinterpret the variant.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001172266	SCV001193436	pathogenic	Chromosome 4q21 deletion syndrome	2019-12-02	no assertion criteria provided	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001172267	SCV001193438	pathogenic	Williams syndrome	2019-12-02	no assertion criteria provided	clinical testing
Department of Maternal-Fetal Biology, National Research Institute for Child Health and Development	RCV001293866	SCV001424911	pathogenic	Autoinflammatory syndrome, familial, Behcet-like	2020-07-29	no assertion criteria provided	research	This deletion was detected by copy number variation analysis conducted with WES data and SNP array. The information of this deletion was taken from the SNP array results.
Division of Human Genetics, Children's Hospital of Philadelphia	RCV001251455	SCV001427082	likely pathogenic	Alveolar capillary dysplasia with pulmonary venous misalignment	2018-11-27	no assertion criteria provided	clinical testing
Blueprint Genetics	RCV001251576	SCV001427356	pathogenic	Retinitis pigmentosa 3		no assertion criteria provided	clinical testing
New York Genome Center	RCV001255130	SCV001431224	uncertain significance	not provided	2019-12-13	no assertion criteria provided	clinical testing
New York Genome Center	RCV001255131	SCV001431225	uncertain significance	not provided	2020-02-05	no assertion criteria provided	clinical testing	The ChrX:31569600-32099659dup variant duplicates exons 45-55 of the DMD gene and is predicted to lead to an in-frame consequence. This variant is absent from gnomAD SVs v2.1. Three individuals have been reported in the literature with duplication of exons 45-55 including one individual with a clinical diagnosis of Duchenne muscular dystrophy or Becker muscular dystrophy (not specified) [PMID: 16917894], as well as one female with DMD like phenotype with onset at 2 years of age [PMID: 30816495], and one female with BMD like phenotype onset in early childhood [PMID: 30816495]. While in silico algorithms predict this to be an in-frame duplication, the exact functional consequence of the duplication observed in this individual is uncertain.
Institute of Human Genetics, Heidelberg University	RCV001260591	SCV001433869	pathogenic	Autism spectrum disorder due to AUTS2 deficiency	2020-09-28	no assertion criteria provided	clinical testing	This deletion encompasses exon 6 of AUTS2. Exon 6 deletions have previously been described to cause C-terminal protein disruption by frameshift and severe expression of AUTS2 syndrome (PMID 23332918, PMID 27531620, PMID 27075013). The variant has not been detected in control populations (PMID 23332918).
University of Washington Center for Mendelian Genomics, University of Washington	RCV001257920	SCV001434729	likely pathogenic	not provided		no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV001257921	SCV001434730	likely pathogenic	not provided		no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV001257979	SCV001434792	likely pathogenic	Familial aplasia of the vermis		no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV001257993	SCV001434806	likely pathogenic	Congenital cerebellar hypoplasia		no assertion criteria provided	research
Pediatric Neurology and Rare Diseases Department, Hospital Sant Joan de Deu	RCV001268961	SCV001441594	pathogenic	SSR4-congenital disorder of glycosylation	2020-11-10	no assertion criteria provided	clinical testing	Deletions including this gene have been reported by Ng et al 2015, Human Mutation (DOI: 10.1002/humu.22856)
Laboratoire de Génétique Moléculaire, CHU Bordeaux	RCV001267824	SCV001443813	uncertain significance	Spastic paraplegia	2020-09-08	no assertion criteria provided	clinical testing	The 2p22.3 deletion, including SPAST from exons 4 to 17, was identified at the mosaic state in an asymptomatic 68 years-old man. Mosaic rate was estimated at 40% of blood lymphocytes (log ratio= -0,31). His son presented the deletion at the constitutional state, with a spastic paraplegia phenotype.
Laboratory of Prof. Karen Avraham, Tel Aviv University	RCV001268958	SCV001448202	pathogenic	Stapes ankylosis with broad thumbs and toes	2020-10-18	no assertion criteria provided	case-control	Congenital conductive hearing loss and hyperopia
Provincial Medical Genetics Program of British Columbia, University of British Columbia	RCV001270910	SCV001449042	benign	Duchenne muscular dystrophy	2020-12-07	no assertion criteria provided	clinical testing	Using long-read whole genome sequencing on the healthy female proband, we defined the duplication (ChrX:30939526-31362638) as a direct repeat inserted downstream of DMD. Analysis of each DMD allele showed an intact DMD locus on each allele. The healthy female proband has 3 copies of FTHL17 and exons 62-79 of DMD transcript NM_0000109.3. Haplotype-specific alignment and analysis of the short-read sequences did not identify a DMD pathogenic or likely pathogenic variant and confirmed the breakpoint identified by long read sequencing. This determined that the duplication did not disrupt the DMD gene. This variant was also detected in the female proband's healthy adult brother who is asymptomatic, which supports our findings that the Xp21.2 duplication is not pathogenic.
The Raphael Recanati Genetics Institute, Rabin Medical Center	RCV001553786	SCV001478902	benign	Hearing impairment		no assertion criteria provided	clinical testing
The Raphael Recanati Genetics Institute, Rabin Medical Center	RCV001553787	SCV001478903	benign	Hearing impairment		no assertion criteria provided	clinical testing
The Raphael Recanati Genetics Institute, Rabin Medical Center	RCV001553788	SCV001478904	benign	Hearing impairment		no assertion criteria provided	clinical testing
University of Washington Center for Mendelian Genomics, University of Washington	RCV001291440	SCV001479942	likely pathogenic	Neurodevelopmental disorder		no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV001291441	SCV001479943	likely pathogenic	Neurodevelopmental disorder		no assertion criteria provided	research
Institute of Human Genetics, University of Leipzig Medical Center	RCV001293366	SCV001481818	pathogenic	Epilepsy; Intellectual disability	2021-02-25	no assertion criteria provided	clinical testing	The copy number variant arr[GRCh37] 22q11.21(18889490_21463730)x1 was identified in an individual with Epilepsy + NDD. Inheritance was de novo (heterozygous). The variant was reviewed according to current ClinGen recommendations and classified as Pathogenic (criteria: 1A(0), 2A(1), 3C(0.9), 4B(0.15), 5A(0.15), Total score=2.2).
Institute of Human Genetics, University of Leipzig Medical Center	RCV001293367	SCV001481820	pathogenic	Intellectual disability	2021-02-25	no assertion criteria provided	clinical testing	The copy number variant arr[GRCh37] 2q37.2q37.3(237201756_243048760)x1 was identified in an individual with NDD. Inheritance was not applicable (heterozygous). The variant was reviewed according to current ClinGen recommendations and classified as Pathogenic (criteria: 1A(0), 2A(1), 3C(0.9), 5H(0.3), Total score=2.2).
Institute of Human Genetics, University of Leipzig Medical Center	RCV001293368	SCV001481821	pathogenic	Intellectual disability	2021-02-25	no assertion criteria provided	clinical testing	The copy number variant arr[GRCh37] 22q13.2(42356886_43684002)x1 dn was identified in an individual with NDD. Inheritance was de novo (heterozygous). The variant was reviewed according to current ClinGen recommendations and classified as Pathogenic (criteria: 1A(0), 2A(1), 3C(0.9), 4C(0.15), 5A(0.15), Total score=2.2).
Institute of Human Genetics, University of Leipzig Medical Center	RCV001293373	SCV001481822	pathogenic	Intellectual disability	2021-02-25	no assertion criteria provided	clinical testing	The copy number variant arr[GRCh37] 9q22.32q31.1(97834573_107199088)x1 was identified in an individual with NDD. Inheritance was de novo (heterozygous). The variant was reviewed according to current ClinGen recommendations and classified as Pathogenic (criteria: 1A(0), 2A(1), 3C(0.9), 4B(0.15), 5A(0.15), Total score=2.2).
Institute of Human Genetics, University of Leipzig Medical Center	RCV001293372	SCV001481824	pathogenic	Intellectual disability	2021-02-25	no assertion criteria provided	clinical testing	The variant chr16:g.(28498776_28497972)_(28497667_28495440)del, CLN3(NM_000086.2):c.(460+1_461-1)_(677+1_678-1)del,p.0? was identified in an individual with NDD. Inheritance was paternal & maternal (homozygous). The variant was reviewed according to current ACMG recommendations and classified as Pathogenic (criteria: PVS1_Strong, PM2_Supporting, PM3_Moderate).
Institute of Human Genetics, University of Leipzig Medical Center	RCV001293371	SCV001481826	pathogenic	Intellectual disability	2021-02-25	no assertion criteria provided	clinical testing	The copy number variant arr[GRCh37] 15q11.1q11.2(20612840_23272733)x1 was identified in an individual with NDD. Inheritance was not applicable (heterozygous). The variant was reviewed according to current ClinGen recommendations and classified as Pathogenic (criteria: 1A(0), 2A(1), 3C(0.9), 4E(0.1), 5F(0), Total score=2).
Institute of Human Genetics, University of Leipzig Medical Center	RCV001293370	SCV001481827	pathogenic	Intellectual disability	2021-02-25	no assertion criteria provided	clinical testing	The copy number variant arr[GRCh37] 22q11.21(18886915_21463730)x1 was identified in an individual with NDD. Inheritance was de novo (heterozygous). The variant was reviewed according to current ClinGen recommendations and classified as Pathogenic (criteria: 1A(0), 2A(1), 3C(0.9), 4B(0.15), 5A(0.15), Total score=2.2).
Institute of Human Genetics, University of Leipzig Medical Center	RCV001293378	SCV001481828	pathogenic	Intellectual disability	2021-02-25	no assertion criteria provided	clinical testing	The copy number variant arr[GRCh37] 2q11.1q11.2(96737083_98193473)x1 was identified in an individual with NDD. Inheritance was not applicable (heterozygous). The variant was reviewed according to current ClinGen recommendations and classified as Pathogenic (criteria: 1A(0), 2A(1), 3A(0), 4M(0.3), 5F(0), Total score=1.3).
Institute of Human Genetics, University of Leipzig Medical Center	RCV001293377	SCV001481829	pathogenic	Epilepsy	2021-02-25	no assertion criteria provided	clinical testing	The copy number variant arr[GRCh37] 16p13.11(14968859_16363239)x1 mat was identified in an individual with Epilepsy. Inheritance was maternal (heterozygous). The variant was reviewed according to current ClinGen recommendations and classified as Pathogenic (criteria: 1A(0), 2A(1), 3A(0), 5H(0.3), Total score=1.3).
Institute of Human Genetics, University of Leipzig Medical Center	RCV001293376	SCV001481830	pathogenic	Intellectual disability	2021-02-25	no assertion criteria provided	clinical testing	The copy number variant arr[GRCh37] 22q13.2q13.33(42333802_51195728)x1 was identified in an individual with NDD. Inheritance was not applicable (heterozygous). The variant was reviewed according to current ClinGen recommendations and classified as Pathogenic (criteria: 1A(0), 2A(1), 3C(0.9), 4E(0.1), 5F(0), Total score=2).
Institute of Human Genetics, University of Leipzig Medical Center	RCV001293375	SCV001481831	pathogenic	Epilepsy; Intellectual disability	2021-02-25	no assertion criteria provided	clinical testing	The copy number variant arr[GRCh37] 22q11.23(23699269_24992266)x3 was identified in an individual with Epilepsy + NDD. Inheritance was maternal (heterozygous). The variant was reviewed according to current ClinGen recommendations and classified as Pathogenic (criteria: 1A(0), 2A(1), 3A(0), 4K(-0.15), 4M(0.45), 5C(-0.15), Total score=1.15).
Institute of Human Genetics, University of Leipzig Medical Center	RCV001293374	SCV001481832	pathogenic	Epilepsy; Intellectual disability	2021-02-25	no assertion criteria provided	clinical testing	The copy number variant arr[GRCh37] 15q24.2(75596353_76103430)x1 was identified in an individual with Epilepsy + NDD. Inheritance was de novo (heterozygous). The variant was reviewed according to current ClinGen recommendations and classified as Pathogenic (criteria: 1A(0), 2A(1), 3A(0), 4C(0.15), 5A(0.15), Total score=1.3).
Institute of Human Genetics, University of Leipzig Medical Center	RCV001293384	SCV001481833	pathogenic	Intellectual disability	2021-02-25	no assertion criteria provided	clinical testing	The variant chr7:g.(69900768_70163554)_(70163607_70227855)del, AUTS2(NM_015570.3):c.(690+1_691-1)_(742+1_743-1)del,p.0? was identified in an individual with NDD. Inheritance was de novo (heterozygous). The variant was reviewed according to current ACMG recommendations and classified as Pathogenic (criteria: PVS1_VeryStrong, PS2_Moderate, PM2_Supporting).
Institute of Human Genetics, University of Leipzig Medical Center	RCV001293383	SCV001481835	pathogenic	Intellectual disability	2021-02-25	no assertion criteria provided	clinical testing	The variant chr14:g.(88429727_88417093)_(88399358_86089631)del, GALC(NM_000153.3):c.(1161+1_1162-1)_(*1718_?)del,p.? was identified in an individual with NDD. Inheritance was paternal (heterozygous). The variant was reviewed according to current ACMG recommendations and classified as Pathogenic (criteria: PSV1_VeryStrong, PM2_Supporting, PM3_Moderate, PP4_Supporting). This variant was identified in a compound heterozygous state with the variant NM_000153.4(GALC):c.1586C>T (p.Thr529Met) (Variation ID: 370073).
Institute of Human Genetics, University of Leipzig Medical Center	RCV001293379	SCV001481836	pathogenic	Epilepsy; Intellectual disability	2021-02-25	no assertion criteria provided	clinical testing	The copy number variant arr[GRCh37] 9q34.3(139764148_141066491)x1 was identified in an individual with NDD + Epilepsy. Inheritance was de novo (heterozygous). The variant was reviewed according to current ClinGen recommendations and classified as Pathogenic (criteria: 1A(0), 2A(1), 3C(0.9), 4B(0.3), 5A(0.3), Total score=2.5).
Institute of Human Genetics, University of Leipzig Medical Center	RCV001293381	SCV001481839	pathogenic	Epilepsy; Intellectual disability	2021-02-25	no assertion criteria provided	clinical testing	The variant chr16:g.(78149052_78198079)_(78198187_78420756)del, WWOX(NM_016373.3):c.(409+1_410-1)_(516+1_517-1)del,p.0? was identified in an individual with Epilepsy + NDD. Inheritance was maternal (heterozygous). The variant was reviewed according to current ACMG recommendations and classified as Pathogenic (criteria: PSV1_VeryStrong, PM2_Supporting, PM3_Moderate). This variant was identified in a compound heterozygous state with the variant NM_016373.4(WWOX):c.184G>T (p.Gly62Ter) (Variation ID: 976436).
Institute of Human Genetics, University of Leipzig Medical Center	RCV001293382	SCV001481840	pathogenic	Intellectual disability	2021-02-25	no assertion criteria provided	clinical testing	The variant chr11:g.(11835569_118359328)_(118372573_118373112)del was identified in an individual with NDD + Epilepsy. Inheritance was de novo (heterozygous). The variant was reviewed according to current ACMG recommendations and classified as Pathogenic (criteria: PVS1_VeryStrong, PS2_Moderate, PM2_Supporting).
Bone Marrow Failure laboratory, Queen Mary University London	RCV001312238	SCV001502674	likely pathogenic	Thrombocytopenia	2021-01-20	no assertion criteria provided	research	This heterozygous, structural deletion variant of the 5' end of RUNX1, was identified in a male with thrombocytopenia. In his family there are 8 affected members over three generations; four had TCP in four it evolved to AML (PMID:32098966). The deletion was shown to segregate in three of these affected relatives.
Bone Marrow Failure laboratory, Queen Mary University London	RCV001312239	SCV001502675	likely pathogenic	Acute myeloid leukemia	2021-01-20	no assertion criteria provided	research	This heterozygous, structural deletion variant of the 5' end of RUNX1, was identified in a male that developed AML (M2 subtype with trisomy19) at age 13 yrs (PMID:32098966).
Bone Marrow Failure laboratory, Queen Mary University London	RCV001312240	SCV001502676	likely pathogenic	Acute myeloid leukemia	2021-01-20	no assertion criteria provided	research	This heterozygous, structural deletion variant of the 5' end of RUNX1, was identified in a male that had a platelet defect from the age of 6 years and then developed AML aged 13 years (PMID:32098966). His father had platelet storage pool disorder but has not been tested.
Dermatology Genetics Laboratory, Dalhousie University	RCV001358803	SCV001547198	pathogenic	Basan syndrome		no assertion criteria provided	research	Heterozygous loss of function variants in the skin-specific isoform of SMARCAD1 are associated with three allelic syndromes; isolated adermatoglyphia, Basan, and Huriez (Nousbeck et al., 2011; Burger et al., 2011; Li, et al., 2016; Marks et al., 2014; Valentin et al., 2018). This complex variant results in the removal of the first 9 exons of SMARCAD1 and exon 1 of its skin-specific isoform. It segregates with Basan phenotype in 12 affected members of a 5-generation family. The variant includes a deletion of ~50.9-kb (hg38 chr4:94,203365-94,254,728) and a duplication of ~23.4-kb (hg38 chr4:94,175,790-94, 199182). The duplication is an inverted non-tandem duplication. The inverted copy is inserted downstream at position chr4:94,203365.
Daryl Scott Lab, Baylor College of Medicine	RCV001374461	SCV001571333	pathogenic	See cases	2021-04-16	no assertion criteria provided	clinical testing
Suna and Inan Kirac Foundation Neurodegeneration Research Laboratory, Koc University	RCV001420678	SCV001593258	pathogenic	Juvenile-onset Parkinson disease	2021-05-12	no assertion criteria provided	research
University Health Network, Princess Margaret Cancer Centre	RCV001527475	SCV001738493	pathogenic	Ovarian neoplasm	2021-03-19	no assertion criteria provided	clinical testing
University Health Network, Princess Margaret Cancer Centre	RCV001527477	SCV001738495	pathogenic	Acquired polycythemia vera; Endometrial serous adenocarcinoma	2021-03-19	no assertion criteria provided	clinical testing
University Health Network, Princess Margaret Cancer Centre	RCV001527483	SCV001738503	pathogenic	Familial cancer of breast	2021-03-19	no assertion criteria provided	clinical testing
University of Washington Center for Mendelian Genomics, University of Washington	RCV001751799	SCV001761940	likely pathogenic	Thoracic aortic aneurysm		no assertion criteria provided	research
University of Washington Center for Mendelian Genomics, University of Washington	RCV001543415	SCV001761975	likely pathogenic	Acheiropodia		no assertion criteria provided	research
School of Medicine, Southern Illinois University	RCV001837015	SCV001786696	pathogenic	Loeys-Dietz syndrome 4	2021-08-15	no assertion criteria provided	clinical testing
School of Medicine, Southern Illinois University	RCV001837011	SCV001786697	pathogenic	Loeys-Dietz syndrome 4	2021-08-15	no assertion criteria provided	clinical testing
School of Medicine, Southern Illinois University	RCV001837012	SCV001786698	pathogenic	Loeys-Dietz syndrome 4	2021-08-15	no assertion criteria provided	clinical testing
School of Medicine, Southern Illinois University	RCV001837013	SCV001786699	pathogenic	Loeys-Dietz syndrome 4	2021-08-15	no assertion criteria provided	clinical testing
School of Medicine, Southern Illinois University	RCV001837014	SCV001786700	pathogenic	Loeys-Dietz syndrome 4	2021-08-15	no assertion criteria provided	clinical testing
Undiagnosed Diseases Network, NIH	RCV001592787	SCV001827205	uncertain significance	Kleefstra syndrome 2	2021-03-03	no assertion criteria provided	clinical testing
Institute of Science, Banaras Hindu University	RCV001785447	SCV002025778	pathogenic	X-linked intellectual disability-cerebellar hypoplasia syndrome	2021-11-23	no assertion criteria provided	research	Pathogenic variants in the Oligophrenin 1 gene (OPHN1) cause an X-linked intellectual disability syndrome with a phenotype typically consisting of cerebellar hypoplasia, ventriculomegaly, seizures, facial dysmorphism, speech delay and sometimes behavioral difficulties. We describe a male patient with global developmental delay, and cerebellar hypoplasia and other neuroanatomical findings suggestive of a Dandy-Walker malformation. The clinical pontocerebellar hypoplasia sequencing panel revealed a partial duplication from exon 7 to exon 15 in OPHN1, which was maternally inherited. PCR-Sanger sequencing of cDNA showed a truncating frameshift in the OPHN1 transcript. Further, transcript level analysis of OPHN1 showed a 75% reduction in the total expression in the patient in comparison to controls. Presumably this leads to a similar reduction in the level of OPHN1 protein resulting in the observed phenotype. This is the first report of a partial duplication of exons 7-15 in OPHN1 in a patient with strabismus, speech delay, dysmorphic facial features, epilepsy, an autism-like phenotype, and developmental delay.
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV001787257	SCV002029059	pathogenic	Intellectual disability	2021-12-02	no assertion criteria provided	clinical testing	de novo Affects TCF4
Génétique des Maladies du Développement, Hospices Civils de Lyon	RCV001787258	SCV002029060	pathogenic	Intellectual disability, mild	2021-12-02	no assertion criteria provided	clinical testing	Inherited from affected mother. Affects TCF4
Genome Sciences Centre, British Columbia Cancer Agency	RCV001815152	SCV002062057	uncertain significance	Adrenal cortex carcinoma	2022-01-20	no assertion criteria provided	research
Genome Sciences Centre, British Columbia Cancer Agency	RCV001815154	SCV002062059	uncertain significance	Adrenal cortex carcinoma	2022-01-20	no assertion criteria provided	research
Genome Sciences Centre, British Columbia Cancer Agency	RCV001815155	SCV002062060	uncertain significance	Adrenal cortex carcinoma	2022-01-20	no assertion criteria provided	research
Odermatt lab, University of Bonn	RCV002287905	SCV002498762	uncertain significance	X-linked intellectual disability, Stocco dos Santos type	2022-04-11	no assertion criteria provided	research
Odermatt lab, University of Bonn	RCV002287906	SCV002498763	uncertain significance	X-linked intellectual disability, Stocco dos Santos type	2022-04-11	no assertion criteria provided	research
IU Genetic Testing Laboratories, Indiana University School of Medicine	RCV002251690	SCV002520684	likely pathogenic	Delayed speech and language development	2020-09-30	no assertion criteria provided	clinical testing	Deletions of this region have been described in individuals with variable neurodevelopmental phenotypes including speech and language impairment. This deletion does not encompass the FOXP2 gene, which has been strongly associated with speech and language impairment and is included in the deleted region for the majority of published cases (PMID: 17330859). However, one recent case report describes a 4.7 Mb deletion downstream of FOXP2 in three family members presenting with variable speech, language and neurodevelopmental phenotypes; the proband in this family also had microcephaly, minor facial dysmorphism including prominent ears and wide mouth (PMID: 32885567). Another published case of a deletion in this region that does not include FOXP2, as well as a review of several overlapping 7q31 deletions listed in the DECIPHER database, suggested consistent features of delayed speech and language development (PMID: 27075776). It was hypothesized that the deletion results in a position effect on the nearby FOXP2 gene expression.
Department of Endocrinology and Genetics, Fuzhou Children’s Hospital of Fujian Medical University	RCV002255086	SCV002520686	pathogenic	Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans	2022-03-18	no assertion criteria provided	clinical testing	A monozygotic 3.1-year-old Chinese male, presented with a chief complaint of short stature at our clinic. He was delivered at 36 weeks and four days of gestation with a birth weight of 1.5kg (-4.09SD) and a birth length of 42.0 cm (-2.98SD). After birth, he could not reach milestones for his age. There was also midface hypoplasia, frontal bossing, flat nasal bridge, low-set ears, short neck, and low height (-3.18SD).The height of his father was 172 .0cm (-0.11SD), and his mother was 149.0cm (-2.15SD), his aunt was 148.0 cm (-2.33SD) in height.
Department of Endocrinology and Genetics, Fuzhou Children’s Hospital of Fujian Medical University	RCV002250442	SCV002520699	pathogenic	Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans	2022-02-26	no assertion criteria provided	clinical testing
Department of Endocrinology and Genetics, Fuzhou Children’s Hospital of Fujian Medical University	RCV002251311	SCV002520700	pathogenic	Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans		no assertion criteria provided	clinical testing
Department of Endocrinology and Genetics, Fuzhou Children’s Hospital of Fujian Medical University	RCV002255085	SCV002520702	uncertain risk allele	Short stature and advanced bone age, with or without early-onset osteoarthritis and/or osteochondritis dissecans		no assertion criteria provided	clinical testing	The proband was a 7-year-11-month-old boy. His height was 114.4cm (-2.85SD) and weight was 20.0kg. Physical examination revealed midface hypoplasia, flat nasal bridge, and brachydactyly. A deletion variant (ACAN c.2897_2953del, p. Ser968_Ala986del) was detected, inherited from his mother. His father’s height was 167.0cm (-0.93SD), his mother was 160.0cm (-0.11SD), and his grandmother was 150. 0cm (-1.96SD).
Cytogenetics, Genetics Associates, Inc.	RCV002292428	SCV002568446	pathogenic	See cases		no assertion criteria provided	clinical testing
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital	RCV002280639	SCV002568904	pathogenic	Potocki-Lupski syndrome		no assertion criteria provided	clinical testing
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital	RCV002280646	SCV002568911	pathogenic	Ring chromosome 7		no assertion criteria provided	clinical testing
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital	RCV002280661	SCV002568926	pathogenic	Heart, malformation of		no assertion criteria provided	clinical testing
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital	RCV002280670	SCV002568933	pathogenic	Turner syndrome		no assertion criteria provided	clinical testing
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital	RCV002280690	SCV002568954	pathogenic	PMP22-RAI1 contiguous gene duplication syndrome		no assertion criteria provided	clinical testing
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital	RCV002280753	SCV002569020	pathogenic	8p inverted duplication/deletion syndrome		no assertion criteria provided	clinical testing
Seattle Children's Hospital Molecular Genetics Laboratory, Seattle Children's Hospital	RCV002280777	SCV002569044	pathogenic	Distal tetrasomy 15q		no assertion criteria provided	clinical testing
Center of Excellence for Medical Genomics, Chulalongkorn University	RCV002283346	SCV002571708	pathogenic	Pyridoxine-dependent epilepsy	2002-09-08	no assertion criteria provided	research
Pele Pequeno Principe Research Institute, Faculdades Pequeno Principe	RCV002286327	SCV002573787	pathogenic	15q11q13 microduplication syndrome	2021-09-09	no assertion criteria provided	clinical testing
Cytogenetics, Genetics Associates, Inc.	RCV002287640	SCV002577391	pathogenic	See cases		no assertion criteria provided	clinical testing
BRCAlab, Lund University	RCV003155994	SCV002588826	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2022-08-26	no assertion criteria provided	clinical testing
Department of Psychiatry, The University of Hong Kong	RCV002463521	SCV002757949	uncertain significance	Schizophrenia	2022-11-11	no assertion criteria provided	case-control
Cincinnati Children's Hospital Medical Center Genetics and Genomics Diagnostic Laboratory, Cincinnati Children's Hospital Medical Center	RCV003148581	SCV003806696	pathogenic	Familial hemophagocytic lymphohistiocytosis 3	2023-03-02	no assertion criteria provided	clinical testing
Department of Urology, Hunan Children's Hospital	RCV003159083	SCV003845195	likely pathogenic	Hereditary xanthinuria type 1		no assertion criteria provided	research
Genome Sciences Centre, British Columbia Cancer Agency	RCV003229785	SCV003926564	uncertain significance	Adrenal cortex carcinoma	2023-05-08	no assertion criteria provided	research
Chao Lab, Baylor College of Medicine, Texas Children's Hospital	RCV003991563	SCV004041600	likely pathogenic	PPFIA3-related disorder	2023-10-09	no assertion criteria provided	research
Genetics Department, University Hospital of Toulouse	RCV004009748	SCV004042673	likely pathogenic	Anophthalmia-microphthalmia syndrome		no assertion criteria provided	clinical testing	De novo inversion of 3.15 Mb located 100 kb 3’ to the FOXC1 gene. Transcript analysis using conjunctival cells from affected proband has revealed monoallelic expression of FOXC1 consistent with impact on the expression of the gene.
Center for Medical Genetics, Keio University School of Medicine	RCV003600463	SCV004177229	pathogenic	Cockayne syndrome type 1		no assertion criteria provided	research
Undiagnosed Diseases Network, NIH	RCV003493385	SCV004242197	uncertain significance	Neurodevelopmental disorder with microcephaly, hypotonia, nystagmus, and seizures	2023-04-28	no assertion criteria provided	clinical testing
Undiagnosed Diseases Network, NIH	RCV003493388	SCV004242204	uncertain significance	ZNF331 deletion	2023-01-31	no assertion criteria provided	clinical testing	Segregates in one family in 4 affected cousins, who are children of 3 carrier fathers. Healthy carriers in the family have the deletion on their maternal alleles (except not tested in oldest generation). 2 healthy children of carrier fathers are negative for the deletion.
Institute of Human Genetics, University of Goettingen	RCV003986083	SCV004801911	uncertain significance	Pheochromocytoma	2022-10-20	no assertion criteria provided	clinical testing
Undiagnosed Diseases Network, NIH	RCV003992102	SCV004812035	pathogenic	Nephronophthisis-like nephropathy 1	2024-02-19	no assertion criteria provided	clinical testing
Undiagnosed Diseases Network, NIH	RCV003992105	SCV004812041	pathogenic	Skraban-Deardorff syndrome	2023-08-01	no assertion criteria provided	clinical testing
Undiagnosed Diseases Network, NIH	RCV003992113	SCV004812055	pathogenic	Neurodevelopmental disorder with microcephaly, hypotonia, nystagmus, and seizures		no assertion criteria provided	clinical testing	This deletion was inherited in trans with a CPSF3 missense variant (ClinVar accession number VCV002691767.1)
Monogenic Research Group, University Of Exeter Medical School	RCV003992662	SCV004812182	likely pathogenic	Hyperinsulinemic hypoglycemia, familial, 1	2023-08-01	no assertion criteria provided	research
Blood Transfusion Service Zurich, Swiss Red Cross	RCV004547438	SCV005039009	pathogenic	McLeod neuroacanthocytosis syndrome		no assertion criteria provided	research
OMIM	RCV004560337	SCV005046836	pathogenic	not specified	1984-12-01	no assertion criteria provided	literature only
Molecular Oncology, Hospital Universitario Central de Asturias (HUCA)	RCV004759420	SCV005061301	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2021-05-24	no assertion criteria provided	case-control
Molecular Oncology, Hospital Universitario Central de Asturias (HUCA)	RCV004759421	SCV005061302	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2021-05-24	no assertion criteria provided	case-control
Molecular Oncology, Hospital Universitario Central de Asturias (HUCA)	RCV004759422	SCV005061303	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2021-05-24	no assertion criteria provided	case-control
MOLECULAR BIOLOGY AND HUMAN GENETICS DIVISION, THE UNIVERSITY OF BURDWAN	RCV004595718	SCV005088193	pathogenic	Beta-thalassemia HBB/LCRB	2022-07-26	no assertion criteria provided	clinical testing	The variant causes long deletion in HBB; HBD and HBG1 genomic region. When this variant present with another variant in HBB gene that causes severe anemia, patient require frequent transfusion in few cases Hepatosplenomegaly was observed
MOLECULAR BIOLOGY AND HUMAN GENETICS DIVISION, THE UNIVERSITY OF BURDWAN	RCV004595719	SCV005088194	pathogenic	Beta-thalassemia HBB/LCRB	2022-07-26	no assertion criteria provided	clinical testing	The variant causes long deletion in HBB; HBD genomic region. When this variant present with another variant in HBB gene that causes severe anemia, patient require frequent transfusion in few cases Hepatosplenomegaly was observed
MOLECULAR BIOLOGY AND HUMAN GENETICS DIVISION, THE UNIVERSITY OF BURDWAN	RCV004595720	SCV005088195	pathogenic	Beta-thalassemia HBB/LCRB	2022-07-26	no assertion criteria provided	clinical testing	The variant causes long deletion in HBB; HBD genomic region. When this variant present with another variant in HBB gene that causes severe anemia, patient require frequent transfusion in few cases Hepatosplenomegaly was observed
MOLECULAR BIOLOGY AND HUMAN GENETICS DIVISION, THE UNIVERSITY OF BURDWAN	RCV004595721	SCV005088196	pathogenic	Beta-thalassemia HBB/LCRB	2022-07-26	no assertion criteria provided	clinical testing	The variant causes long deletion in HBB;HBD; HBG1;HBG2 and HBE1 genomic region. When this variant present with another variant in HBB gene that causes severe anemia, patient require frequent transfusion in few cases Hepatosplenomegaly was observed
MOLECULAR BIOLOGY AND HUMAN GENETICS DIVISION, THE UNIVERSITY OF BURDWAN	RCV004595722	SCV005088197	pathogenic	Beta-thalassemia HBB/LCRB	2022-07-26	no assertion criteria provided	clinical testing	The variant causes long deletion of entire beta globin gene cluster, ( HBB; HBD;HBG1;HBG2;HBE1, OR51B4) genomic region. When this variant present with another variant in HBB gene that causes severe anemia, patient require frequent transfusion in few cases Hepatosplenomegaly was observed
Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen	RCV004698950	SCV005200689	pathogenic	Russell-Silver syndrome		no assertion criteria provided	clinical testing	The duplication of the NSD1 gene has been reported in a Patient with SRS before (Sachwitz et al. 2017). According to the ClinGen and ACMG classfication criteria the duplication was ranked pathogenic.
Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen	RCV004698951	SCV005200690	uncertain significance	11p13 microduplication syndrome		no assertion criteria provided	clinical testing	The duplication of the 11p13.3 region was recently identified as a potential new syndrom by Amin et al. (2024). The CNV was ranked as Variant of uncertain significance by the ClinGen and ACMG criteria.
Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen	RCV004698952	SCV005200691	uncertain significance	Chromosome 15q11.2 deletion syndrome		no assertion criteria provided	clinical testing	Deletions within the breakpoint BP1 and BP2 on chromosome 15 are associated with the 15q11.2 deletion syndrome. The CNV was inherited from the unaffected mother, however inheritance from a healthy parent has been desribed in the literature before. The CNV was ranked as variant of unknown significance due to the inheritance from an unaffected parent.
Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Pirogov Russian National Research Medical University	RCV004727573	SCV005326553	pathogenic	See cases	2024-07-08	no assertion criteria provided	research	We classified this CNV as Pathogenic regarding criteria. 1-A Contains protein-coding or other known functionally important elements, 2A - Overlap with established HI/LOF-sensitive genes or genomic regions, 2H - Haploinsufficient predictors suggest that AT LEAST ONE gene in the interval is haploinsufficient (HI), 3C - Number of protein-coding RefSeq genes wholly or partially included in the CNV region is 35 or more, 4L - Case-control and population evidence. [Riggs ER, Andersen EF, Cherry AM, et al. Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) [published correction appears in Genet Med. 2021 Nov;23(11):2230. doi: 10.1038/s41436-021-01150-9]. Genet Med. 2020;22(2):245-257. doi:10.1038/s41436-019-0686-8]
Undiagnosed Diseases Network, NIH	RCV004759753	SCV005368683	pathogenic	Chromosome 15q11.2 deletion syndrome	2024-06-10	no assertion criteria provided	clinical testing
Undiagnosed Diseases Network, NIH	RCV004759761	SCV005368696	pathogenic, low penetrance	Epilepsy, familial focal, with variable foci 1	2023-08-16	no assertion criteria provided	clinical testing

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