Submissions for variant Single allele

Total submissions: 5451

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 Monogenic Diabetes Variant Curation Expert Panel	RCV001843397	SCV002102527	uncertain significance	Monogenic diabetes	2022-03-04	reviewed by expert panel	curation	The c.-258A>G variant in the HNF1 homeobox A gene, HNF1A, is located in the promoter of NM_000545.8. This variant is located within a conserved region of the DNA binding domain (codons 107-174 and 201-280) of HNF1A, which is defined as critical for the protein’s function by the ClinGen MDEP (PM1_Supporting). Additionally, this variant was identified in an individual with a clinical history highly specific for HNF1A-MODY (MODY probability calculator result >50%, negative genetic testing for HNF4A) (PP4; internal lab contributor). In summary, c.-258A>G 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, PP4.
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.
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.
Developmental Genetics Unit,King Faisal Specialist Hospital & Research Centre	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	RCV000203496	SCV000258330	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	RCV000203460	SCV000258354	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
Baylor Genetics	RCV000240814	SCV000258399	pathogenic	Progressive familial intrahepatic cholestasis type 1	2015-12-17	criteria provided, single submitter	clinical testing	This variant was found in compound heterozygous status with another pathogenic insertion variant in two affected members of a Caucasian family
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
Ludwig Lab, Institute of Human Genetics, University Hospital Bonn	RCV000417195	SCV000262654	likely pathogenic	Currarino triad		criteria provided, single submitter	research	Large de novo duplication in a patient with negative family history.
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	RCV000210452	SCV000266536	pathogenic	Loeys-Dietz syndrome 4		criteria provided, single submitter	research
Baylor-Hopkins Center for Mendelian Genomics,Johns Hopkins University	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	RCV000235059	SCV000292312	likely pathogenic	Charcot-Marie-Tooth disease type 1B	2015-09-17	criteria provided, single submitter	research	This duplication was identified in a patient with peripheral neuropathy. There is a report in the literature of MPZ duplication in an individual with peripheral neuropathy (PMID:21787890).
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
Illumina Laboratory Services,Illumina	RCV000393096	SCV000483466	likely benign	MYH7-related skeletal myopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services,Illumina	RCV000304800	SCV000483467	likely benign	Myosin storage myopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services,Illumina	RCV000341222	SCV000483468	likely benign	Scapuloperoneal myopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services,Illumina	RCV000393119	SCV000483469	likely benign	Left ventricular noncompaction cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services,Illumina	RCV000310759	SCV000483470	likely benign	Dilated Cardiomyopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services,Illumina	RCV000365436	SCV000483471	likely benign	Hypertrophic cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services,Illumina	RCV000261807	SCV000483973	likely benign	Myosclerosis	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services,Illumina	RCV000330899	SCV000483974	likely benign	Collagen 6-related myopathy	2016-06-14	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
Centre for Mendelian Genomics,University Medical Centre Ljubljana	RCV000414960	SCV000492733	pathogenic	Renal cyst; Pancreatic cysts	2015-09-23	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 5’-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
Counsyl	RCV000496588	SCV000579478	pathogenic	Spinal muscular atrophy, type II; Kugelberg-Welander disease; Werdnig-Hoffmann disease; Spinal muscular atrophy, type IV	2016-11-08	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	-α3.7 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, Klinikum rechts der Isar	RCV000505401	SCV000599662	pathogenic	Familial X-linked hypophosphatemic vitamin D refractory rickets	2013-11-06	criteria provided, single submitter	clinical testing
Institute of Human Genetics, Klinikum rechts der Isar	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
Undiagnosed Diseases Network, NIH	RCV000551008	SCV000622149	uncertain significance	Brown-Vialetto-van Laere syndrome 1	2016-03-02	criteria provided, single submitter	clinical testing	Clinically diagnosed with riboflavin transporter deficiency; patient responded to high dose vitamin B2 treatment.
Invitae	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.
Invitae	RCV000527667	SCV000623936	likely pathogenic	Primary ciliary dyskinesia	2017-02-06	criteria provided, single submitter	clinical testing	This variant is a gross duplication of the genomic region encompassing exons 7-14 of the DNAH11 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. A copy number variant encompassing the same exons of DNAH11 occurs with a second rare variant (p.Arg3429Ser) in an individual with primary ciliary dyskinesia (PMID:26139845). While it is unknown if these two variants are on the same or opposite chromosomes, this observation suggests a duplication of exons 7-14 may contribute to the cause of disease. In summary, this variant is a rare exon level duplication, and a similar copy number variant has been reported in an affected individual. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Invitae	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.
Invitae	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. 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. ClinVar contains an entry for MSH2 duplications of exons 5-7 (Variation ID: 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.
Invitae	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.
Invitae	RCV000544111	SCV000625805	uncertain significance	Duchenne muscular dystrophy	2017-08-08	criteria provided, single submitter	clinical testing	This variant is a gross duplication of the genomic region encompassing exon 30 of the DMD 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 individuals with DMD-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 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.
Invitae	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.
Invitae	RCV000529549	SCV000628836	uncertain significance	Neurofibromatosis, type 2	2017-05-02	criteria provided, single submitter	clinical testing	This variant is a gross duplication of the genomic region encompassing exons 13-16 of the NF2 gene. The 5' boundary is likely confined to intron 12. 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 NF2-related disease. In summary, the exact genomic location of this variant is unknown and the impact of this duplication on NF2 protein function has not been established. Therefore, it has been classified as a Variant of Uncertain Significance.
Invitae	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.
Invitae	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.
Invitae	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  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.
Invitae	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.
Invitae	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.
Invitae	RCV000545391	SCV000636113	benign	Nephronophthisis	2017-02-10	criteria provided, single submitter	clinical testing
Invitae	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.
Invitae	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.
Invitae	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
Invitae	RCV000543941	SCV000646080	uncertain significance	Progressive familial heart block type IB	2018-01-04	criteria provided, single submitter	clinical testing
Invitae	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.
Invitae	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.
Invitae	RCV000547325	SCV000650689	uncertain significance	Idiopathic Pulmonary Fibrosis; 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
Invitae	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.
Invitae	RCV000552669	SCV000652820	uncertain significance	Young adult-onset distal hereditary motor neuropathy	2017-06-05	criteria provided, single submitter	clinical testing	This variant is a gross duplication of the genomic region encompassing exon 10 of the DNAJB2 gene. The 5' boundary is likely confined to intron 9. The 3' end of this event is unknown as it extends beyond the assayed region for this gene and therefore may encompass additional genes.  There is evidence that this duplication is in tandem. This duplication has not been reported in the literature in individuals with a DNAJB2-related disease. Experimental studies are not available for this copy number variant, and the functional significance of the duplicated exon is currently unknown. In summary, this is a tandem duplication with uncertain impact on DNAJB2 function.  The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Invitae	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.
Invitae	RCV000530783	SCV000654833	uncertain significance	Arrhythmogenic right ventricular dysplasia 13	2017-04-07	criteria provided, single submitter	clinical testing	This variant is a gross duplication of the genomic region encompassing exon 7 of the CTNNA3 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 CTNNA3-related disease. In summary, the exact genomic location of this variant is unknown and the impact of this duplication on CTNNA3 protein function has not been established. Therefore, it has been classified as a Variant of Uncertain Significance.
Invitae	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 Institute Rare Disease Group, Broad Institute	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
GeneDx	RCV000603650	SCV000719684	likely benign	not specified	2017-05-26	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
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
Counsyl	RCV000668947	SCV000793630	uncertain significance	Galactosylceramide beta-galactosidase deficiency	2017-08-25	criteria provided, single submitter	clinical testing
Counsyl	RCV000669077	SCV000793779	uncertain significance	Galactosylceramide beta-galactosidase deficiency	2017-08-30	criteria provided, single submitter	clinical testing
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
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000754990	SCV000803400	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	RCV000677927	SCV000804082	pathogenic	not provided	2018-04-05	criteria provided, single submitter	provider interpretation	This deletion 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 71 Mb terminal duplication of 15q13.2q26.3. 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	RCV000677972	SCV000804127	uncertain significance	not provided	2017-10-07	criteria provided, single submitter	provider interpretation	This 758 kilobase deletion includes four genes - BEND3, PDSS2, SOBP, and SCML4. PDSS2 is associated with primary coenzyme Q10 deficiency -3 (OMIM 614652) and SOBP is associated with intellectual disability, anterior maxillary protrusion and strabismus (OMIM 613671). Smaller overlapping deletions have been reported in DECIPHER, including in an individual with global developmental delay, macrocephaly, and abnormality of the philtrum who was large for gestational age (Case 262370) and an individual with a de novo deletion with a history of autism spectrum disorder, delayed speech and language, intellectual disability, microcephaly, and ventricular septal defect (Case 254740). The deletion in our patient was found to be maternally inherited. The patient's mother reportedly had difficulty in reading and math but did not require additional learning supports. The patient also underwent clinical whole exome sequencing that was negative.
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	RCV000678014	SCV000804169	uncertain significance	Leri-Weill dyschondrosteosis	2018-03-30	criteria provided, single submitter	provider interpretation	This deletion was identified in a 7 year old male with autism spectrum disorder and mild intellectual disability. Parental testing was not completed. This deletion is within the pseudoautosomal region on the short arm terminus of both chromosome X and Y, and involves SHOX enhancers. Of note, this patient is of normal height. Similar deletions have been seen in patients with microcephaly, developmental delays, and/or speech delays. The clinical signifiance of this deletion is currently unclear.
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	RCV000678028	SCV000804183	uncertain significance	not provided	2018-04-13	criteria provided, single submitter	provider interpretation	This deletion was identified in a 7 year old female with short stature, macrocephaly, intellectual disability, global developmental delays, dysmorphic features (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 deleted region contains three genes (RPS6KC1, VASH2, ANGEL2) that are not associated with any known clinical disorders. The clinical significance of this deletion remains unclear at this time. A second maternally-inherited variant was identified through chromosomal microarray, a 10q23.1 duplication of uncertain significance.
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 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 - Viapath,Viapath, Guy's Hospital	RCV000722071	SCV000845782	pathogenic	Split hand-foot malformation	2018-10-31	criteria provided, single submitter	clinical testing	Duplications of this region are associated with split hand/foot malformation 3.
Genetics - Viapath,Viapath, Guy's Hospital	RCV000722072	SCV000845790	pathogenic	Split hand-foot malformation		criteria provided, single submitter	clinical testing	Duplications of this region are associated with split hand/foot malformation 3.
Eurofins NTD LLC (GA)	RCV000730072	SCV000857783	uncertain significance	not provided	2017-10-24	criteria provided, single submitter	clinical testing
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	Nonprogressive cerebellar atxia with intellectual disability	2018-12-17	criteria provided, single submitter	research
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000735905	SCV000864017	benign	Nonprogressive cerebellar atxia with intellectual disability	2018-12-17	criteria provided, single submitter	research
Rare Disease Group, Clinical Genetics, Karolinska Institutet	RCV000735906	SCV000864018	uncertain significance	Nonprogressive cerebellar atxia with intellectual disability	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
Genetics and Personalized Medicine Clinic, Tartu University Hospital	RCV000768549	SCV000898485	pathogenic	Dihydropteridine reductase deficiency	2019-04-20	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	RCV000852268	SCV000900013	likely pathogenic	Hereditary antithrombin deficiency	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	RCV000852274	SCV000900016	uncertain significance	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	RCV000852273	SCV000900024	pathogenic	Macrothrombocytopenia	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 disease	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	RCV000787393	SCV000926355	pathogenic	Multiple fibrofolliculomas	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	RCV000787456	SCV000926418	pathogenic	Colon cancer	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	RCV000787467	SCV000926429	pathogenic	Hypogonadism with anosmia	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 (chr5:127441491‐ 127471419) including an inversion of 34 base pairs (chr5:127441491‐127471419delins34). 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.
GeneDx	RCV001004047	SCV001142746	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.
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 Institute Rare Disease Group, Broad Institute	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 agammaglobulinemia	2019-01-01	criteria provided, single submitter	research
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001027728	SCV001190164	pathogenic	Common variable agammaglobulinemia	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
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	RCV001089822	SCV001245309	pathogenic	Familial hypocalciuric hypercalcemia; Autosomal dominant hypocalcemia 1	2020-01-07	criteria provided, single submitter	clinical testing	This sequence change is an Alu-mediated insertion in exon 7 of the CASR mRNA (c.2643_2644insAlu), causing a frameshift at codon 882 (p.Lys882fs). While this insertion is not anticipated to result in nonsense mediated decay, it is expected to disrupt the C-terminus of the CASR protein. 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). A similar Alu-mediated insertion in CASR have been reported to segregate with familial hypocalciuric hypercalcemia (FHH) and neonatal severe hyperparathyroidism (NSHPT) in three Nova Scotian families (PMID: 7717399, 9217223). Experimental studies have shown that a similar Alu-mediated insertion causes no response to Ca2+ and decreases cell surface expression of the CASR receptor protein in vitro (PMID: 9109436). This Alu-mediated insertion is expected to disrupt a portion of the C-terminal region of the CASR protein containing the intracellular domain (residues 862-1078) (PMID: 20374733). In addition, missense substitutions at codon 886 (p.Arg886Trp and p.Arg886Pro) have been reported in families affected with FHH and have been determined to be likely pathogenic (PMID: 17698911, 11807402, 20798521). This suggests that disruption of this region is causative of disease. For these reasons, this variant has been classified as Pathogenic.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	RCV001089829	SCV001245316	uncertain significance	Melanoma, cutaneous malignant, susceptibility to, 10	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.Tyr1352Alafs*9). 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.Tyr1352Alafs*9) 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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	RCV001089852	SCV001245339	pathogenic	Multiple fibrofolliculomas	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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.
Invitae	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	RCV001090143	SCV001245589	likely pathogenic	FAM177A1-related disorder	2019-10-31	criteria provided, single submitter	clinical testing	Observed in proband and similarly affected sister.
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
Broad Institute Rare Disease Group, Broad Institute	RCV001171638	SCV001250685	uncertain significance	Global developmental delay; Short stature; Macrocephaly; Chorea	2020-05-13	criteria provided, single submitter	research	A heterozygous deletion of the full coding sequence of the RTN4IP1 gene has been identified by our study in an individual with infantile chorea, short stature, macrocephaly, and global developmental delay with regression. This variant was identified in the compound heterozygous state, along with a missense variant of uncertain significance. The break points of this deletion are located in the intronic regions of adjacent genes (5', QRSL; 3' CRYBG1). This variant has not been reported in the literature in any individuals with RTN4IP1-related disease. Loss of function of RTN4IP1 in an autosomal recessive disease has not yet been established based on the criteria laid out in Tayoun, 2018 (PMID: 30192042). In summary, while a whole gene deletion in a recessive gene is suspicious for a pathogenic role, the clinical significance of the chr6:106539151-106629957 deletion is uncertain. (0 points, Riggs 2020).
Turner Lab,Washington University in St. Louis	RCV001174506	SCV001251650	pathogenic	Chromosome 9p deletion syndrome	2020-05-07	criteria provided, single submitter	research	This individual contains a deletion on chromosome 9 (consistent with 9p- syndrome) and also a translocation of a portion of chromosome 13 onto the chromosome 9 with the deletion. The full variant in karyotype form is 46,XX,der(9)t(9;13)(p23;q13).
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	RCV001254216	SCV001430285	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	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
Undiagnosed Diseases Network, NIH	RCV001255606	SCV001432132	likely pathogenic	Intellectual disability, autosomal dominant 56	2020-04-01	criteria provided, single submitter	clinical testing	This deletion was inherited from his father, who has a history of learning disabilities.
Undiagnosed Diseases Network, NIH	RCV001255610	SCV001432136	uncertain significance	Wolf-Hirschhorn like syndrome	2020-05-07	criteria provided, single submitter	clinical testing
Undiagnosed Diseases Network, NIH	RCV001255967	SCV001432743	uncertain significance	ELFN1-related condition	2018-09-18	criteria provided, single submitter	clinical testing
Undiagnosed Diseases Network, NIH	RCV001255970	SCV001432747	pathogenic	Developmental and epileptic encephalopathy, 28	2020-07-08	criteria provided, single submitter	clinical testing
Undiagnosed Diseases Network, NIH	RCV001255971	SCV001432748	pathogenic	Wieacker-Wolff syndrome, female-restricted	2020-05-26	criteria provided, single submitter	clinical testing
Undiagnosed Diseases Network, NIH	RCV001255972	SCV001432749	pathogenic	Koolen-de Vries syndrome	2020-05-29	criteria provided, single submitter	clinical testing
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	RCV001262039	SCV001439417	pathogenic	Telangiectasia, hereditary hemorrhagic, type 1	2018-01-01	criteria provided, single submitter	research	PVS1+PM2+PP4
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.
Dept. Genetics and Cancer, Menzies Institute for Medical Research,University of Tasmania	RCV001376650	SCV001450780	likely benign	Developmental cataract	2020-12-01	criteria provided, single submitter	research
Dept. Genetics and Cancer, Menzies Institute for Medical Research,University of Tasmania	RCV001376651	SCV001450781	likely benign	Developmental cataract	2020-12-01	criteria provided, single submitter	research
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
MNM Diagnostics	RCV001271109	SCV001451953	pathogenic	Familial X-linked hypophosphatemic vitamin D refractory rickets	2019-09-05	criteria provided, single submitter	clinical testing	The variant fulfills the pathogenic criteria due to the following observations. This is a truncating mutation that deletes 6 final exons of the gene, whose loss of function is responsible for disease onset (PVS1). The funcional protein domain is deleted (PM1). Patient's phenotype is specific for a disease with monogenic etiology (PP4), namely hipophosphatemic rickets (XLHR).
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
New York Genome Center	RCV001291765	SCV001480382	uncertain significance	See cases	2020-05-26	criteria provided, single submitter	clinical testing
New York Genome Center	RCV001291766	SCV001480383	uncertain significance	See cases	2020-05-26	criteria provided, single submitter	clinical testing
New York Genome Center	RCV001291781	SCV001480399	uncertain significance	See cases	2020-04-20	criteria provided, single submitter	clinical testing
Undiagnosed Diseases Network, NIH	RCV001310223	SCV001499834	pathogenic	Immunodeficiency 67	2020-11-25	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001311773	SCV001502074	uncertain significance	not provided	2020-08-01	criteria provided, single submitter	clinical testing
MNM Diagnostics	RCV001312195	SCV001502657	pathogenic	Familial X-linked hypophosphatemic vitamin D refractory rickets	2020-01-24	criteria provided, single submitter	clinical testing	This is a hemizygotic deletion spanning two last exons (21-22) of PHEX gene and CBLL2 gene. LOF mutations in PHEX gene are responsible for the X-linked hypophosphatemic rickets (XLHD). Deletion of two last exons were described previously in relation to a XLHD patient (PMID: 19513579). The variant was previously identified as pathogenic (HGMD: CG097917).
Center for Molecular Medicine, Children’s Hospital of Fudan University	RCV001352677	SCV001519656	likely pathogenic	Inflammatory bowel disease 28	2021-01-17	criteria provided, single submitter	clinical testing
GeneDx	RCV001352683	SCV001547262	uncertain significance	not provided	2020-05-20	criteria provided, single submitter	clinical testing	Describes a nucleotide substitution 898 basepairs upstream of the ATG translational start site in the PTEN promoter region; Variants within the PTEN promoter have been observed in individuals with features of Cowden syndrome (Zhou 2003); Has not been previously published as pathogenic or benign to our knowledge; No data available from control populations to assess the frequency of this variant; Also known as c.-897C>T
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
New York Genome Center	RCV001420574	SCV001622889	uncertain significance	See cases	2020-05-07	criteria provided, single submitter	clinical testing
New York Genome Center	RCV001420594	SCV001622911	likely pathogenic	Pitt-Hopkins-like syndrome 2	2020-05-19	criteria provided, single submitter	clinical testing
New York Genome Center	RCV001420608	SCV001622925	uncertain significance	See cases	2020-07-09	criteria provided, single submitter	clinical testing
New York Genome Center	RCV001420629	SCV001622953	pathogenic	15q11q13 microduplication syndrome	2020-06-05	criteria provided, single submitter	clinical testing
New York Genome Center	RCV001420642	SCV001622968	uncertain significance	Febrile seizures, familial, 4	2020-05-19	criteria provided, single submitter	clinical testing
New York Genome Center	RCV001420673	SCV001623006	uncertain significance	not provided	2020-06-03	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
GeneDx	RCV001527755	SCV001738886	benign	not provided	2018-11-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001527805	SCV001738942	likely benign	not provided	2018-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001527809	SCV001738946	likely benign	not provided	2020-01-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001527827	SCV001738965	benign	not provided	2019-04-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001527829	SCV001738967	benign	not provided	2018-11-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001527873	SCV001739016	benign	not provided	2019-09-02	criteria provided, single submitter	clinical testing
GeneDx	RCV001527882	SCV001739025	benign	not provided	2019-05-17	criteria provided, single submitter	clinical testing
GeneDx	RCV001527963	SCV001739114	benign	not provided	2018-11-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001528058	SCV001739219	likely benign	not provided	2019-05-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001528065	SCV001739227	benign	not provided	2021-05-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001530544	SCV001745417	benign	not provided	2021-05-13	criteria provided, single submitter	clinical testing
GeneDx	RCV001530565	SCV001745442	benign	not provided	2021-05-30	criteria provided, single submitter	clinical testing
GeneDx	RCV001530581	SCV001745459	benign	not provided	2018-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001530609	SCV001745492	likely benign	not provided	2020-05-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001530620	SCV001745504	likely benign	not provided	2018-07-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001530625	SCV001745511	likely benign	not provided	2019-01-20	criteria provided, single submitter	clinical testing
GeneDx	RCV001530740	SCV001745637	likely benign	not provided	2019-09-02	criteria provided, single submitter	clinical testing
GeneDx	RCV001530795	SCV001745693	benign	not provided	2018-07-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001530806	SCV001745706	benign	not provided	2018-07-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001530920	SCV001745832	benign	not provided	2018-11-10	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001531296	SCV001746326	likely benign	not provided	2021-05-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001531653	SCV001746886	uncertain significance	not provided	2021-02-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001531665	SCV001746904	likely benign	not provided	2021-05-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001532159	SCV001747588	uncertain significance	not provided	2021-05-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001532567	SCV001748187	likely benign	not provided	2021-03-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001533796	SCV001750657	benign	not provided	2021-05-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001533980	SCV001750863	benign	not provided	2021-05-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001533993	SCV001750878	benign	not provided	2018-06-23	criteria provided, single submitter	clinical testing
GeneDx	RCV001534023	SCV001750911	likely benign	not provided	2018-07-17	criteria provided, single submitter	clinical testing
GeneDx	RCV001534169	SCV001751072	likely benign	not provided	2018-07-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001534191	SCV001751095	benign	not provided	2019-01-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001534262	SCV001751173	benign	not provided	2021-05-22	criteria provided, single submitter	clinical testing
GeneDx	RCV001534283	SCV001751199	likely benign	not provided	2019-08-13	criteria provided, single submitter	clinical testing
GeneDx	RCV001534295	SCV001751212	benign	not provided	2018-11-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001534319	SCV001751239	benign	not provided	2019-02-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001534360	SCV001751283	benign	not provided	2018-11-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001534429	SCV001751358	benign	not provided	2018-06-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001534530	SCV001751470	benign	not provided	2018-06-23	criteria provided, single submitter	clinical testing
GeneDx	RCV001534549	SCV001751490	benign	not provided	2021-05-17	criteria provided, single submitter	clinical testing
GeneDx	RCV001534569	SCV001751512	likely benign	not provided	2018-09-07	criteria provided, single submitter	clinical testing
Kosik Lab, Neuroscience Research Institute,University of California Santa Barbara	RCV001810749	SCV001751549	pathogenic	Alzheimer disease	2021-07-01	criteria provided, single submitter	case-control
GeneDx	RCV001534647	SCV001751580	likely benign	not provided	2019-01-02	criteria provided, single submitter	clinical testing
GeneDx	RCV001534696	SCV001751638	benign	not provided	2018-11-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001534700	SCV001751642	benign	not provided	2018-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001534737	SCV001751680	likely benign	not provided	2019-08-24	criteria provided, single submitter	clinical testing
GeneDx	RCV001534794	SCV001751756	likely benign	not provided	2019-04-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001534905	SCV001751873	benign	not provided	2019-10-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001534935	SCV001751905	benign	not provided	2018-11-16	criteria provided, single submitter	clinical testing
GeneDx	RCV001534943	SCV001751913	benign	not provided	2018-06-23	criteria provided, single submitter	clinical testing
GeneDx	RCV001535046	SCV001752024	likely benign	not provided	2019-10-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001535119	SCV001752106	benign	not provided	2018-07-09	criteria provided, single submitter	clinical testing
GeneDx	RCV001535123	SCV001752110	likely benign	not provided	2018-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001535151	SCV001752141	benign	not provided	2020-06-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001535157	SCV001752147	benign	not provided	2018-07-05	criteria provided, single submitter	clinical testing
GeneDx	RCV001535237	SCV001752232	benign	not provided	2019-01-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001535241	SCV001752238	benign	not provided	2019-08-09	criteria provided, single submitter	clinical testing
GeneDx	RCV001535255	SCV001752253	likely benign	not provided	2019-08-06	criteria provided, single submitter	clinical testing
GeneDx	RCV001535272	SCV001752270	likely benign	not provided	2019-03-25	criteria provided, single submitter	clinical testing
GeneDx	RCV001535300	SCV001752304	benign	not provided	2021-05-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001536184	SCV001752906	benign	not provided	2021-05-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001536186	SCV001752908	benign	not provided	2018-06-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001536239	SCV001752968	benign	not provided	2018-11-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001536371	SCV001753121	benign	not provided	2021-05-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001536394	SCV001753145	benign	not provided	2019-11-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001536480	SCV001753244	benign	not provided	2021-05-19	criteria provided, single submitter	clinical testing
GeneDx	RCV001536553	SCV001753328	likely benign	not provided	2018-06-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001536556	SCV001753331	benign	not provided	2018-07-05	criteria provided, single submitter	clinical testing
GeneDx	RCV001536567	SCV001753345	benign	not provided	2018-12-22	criteria provided, single submitter	clinical testing
GeneDx	RCV001536600	SCV001753380	benign	not provided	2019-09-09	criteria provided, single submitter	clinical testing
GeneDx	RCV001536606	SCV001753386	benign	not provided	2018-06-23	criteria provided, single submitter	clinical testing
GeneDx	RCV001536681	SCV001753476	benign	not provided	2018-06-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001536719	SCV001753521	benign	not provided	2018-06-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001536726	SCV001753529	benign	not provided	2019-08-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001536784	SCV001753592	benign	not provided	2018-07-06	criteria provided, single submitter	clinical testing
GeneDx	RCV001536823	SCV001753633	benign	not provided	2018-12-21	criteria provided, single submitter	clinical testing
GeneDx	RCV001536829	SCV001753639	benign	not provided	2018-07-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001536870	SCV001753681	likely benign	not provided	2020-05-25	criteria provided, single submitter	clinical testing
GeneDx	RCV001536875	SCV001753687	benign	not provided	2018-11-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001536881	SCV001753695	benign	not provided	2018-10-16	criteria provided, single submitter	clinical testing
GeneDx	RCV001536936	SCV001753752	benign	not provided	2018-09-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001536937	SCV001753754	benign	not provided	2018-07-17	criteria provided, single submitter	clinical testing
GeneDx	RCV001536995	SCV001753817	benign	not provided	2021-05-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001537041	SCV001753867	benign	not provided	2018-07-09	criteria provided, single submitter	clinical testing
GeneDx	RCV001537123	SCV001753957	benign	not provided	2019-01-09	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 29588580)
GeneDx	RCV001537142	SCV001753983	benign	not provided	2019-08-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001537207	SCV001754061	benign	not provided	2018-11-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001537211	SCV001754065	benign	not provided	2019-08-13	criteria provided, single submitter	clinical testing
GeneDx	RCV001537287	SCV001754152	benign	not provided	2018-08-09	criteria provided, single submitter	clinical testing
GeneDx	RCV001537296	SCV001754162	benign	not provided	2018-07-05	criteria provided, single submitter	clinical testing
GeneDx	RCV001537309	SCV001754178	benign	not provided	2021-05-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001537402	SCV001754281	likely benign	not provided	2018-10-02	criteria provided, single submitter	clinical testing
GeneDx	RCV001537408	SCV001754291	benign	not provided	2021-06-20	criteria provided, single submitter	clinical testing
GeneDx	RCV001537427	SCV001754311	benign	not provided	2018-07-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001537456	SCV001754341	benign	not provided	2018-11-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001537480	SCV001754367	benign	not provided	2021-05-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001537499	SCV001754386	benign	not provided	2019-08-06	criteria provided, single submitter	clinical testing
GeneDx	RCV001537513	SCV001754400	benign	not provided	2019-11-06	criteria provided, single submitter	clinical testing
GeneDx	RCV001537590	SCV001754489	likely benign	not provided	2019-11-13	criteria provided, single submitter	clinical testing
GeneDx	RCV001537619	SCV001754518	benign	not provided	2019-02-21	criteria provided, single submitter	clinical testing
GeneDx	RCV001537625	SCV001754526	benign	not provided	2021-06-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001537626	SCV001754527	likely benign	not provided	2019-08-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001538087	SCV001755693	benign	not provided	2018-06-19	criteria provided, single submitter	clinical testing
GeneDx	RCV001538119	SCV001755727	likely benign	not provided	2018-08-03	criteria provided, single submitter	clinical testing
GeneDx	RCV001538189	SCV001755803	likely benign	not provided	2019-10-20	criteria provided, single submitter	clinical testing
GeneDx	RCV001538205	SCV001755820	benign	not provided	2021-06-21	criteria provided, single submitter	clinical testing
GeneDx	RCV001538236	SCV001755858	benign	not provided	2018-07-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001538270	SCV001755897	benign	not provided	2021-05-16	criteria provided, single submitter	clinical testing
GeneDx	RCV001538271	SCV001755898	benign	not provided	2018-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001538320	SCV001755953	benign	not provided	2018-11-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001538344	SCV001755983	likely benign	not provided	2018-10-21	criteria provided, single submitter	clinical testing
GeneDx	RCV001538355	SCV001755994	benign	not provided	2018-09-23	criteria provided, single submitter	clinical testing
GeneDx	RCV001538394	SCV001756040	benign	not provided	2021-05-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001538499	SCV001756159	likely benign	not provided	2020-10-20	criteria provided, single submitter	clinical testing
GeneDx	RCV001538504	SCV001756167	benign	not provided	2018-11-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001538520	SCV001756184	benign	not provided	2021-05-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001538595	SCV001756269	benign	not provided	2018-08-17	criteria provided, single submitter	clinical testing
GeneDx	RCV001538630	SCV001756308	benign	not provided	2018-11-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001538688	SCV001756370	benign	not provided	2019-08-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001538722	SCV001756407	benign	not provided	2021-06-20	criteria provided, single submitter	clinical testing
GeneDx	RCV001538745	SCV001756436	benign	not provided	2021-05-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001538881	SCV001756596	benign	not provided	2018-07-03	criteria provided, single submitter	clinical testing
GeneDx	RCV001538917	SCV001756636	benign	not provided	2018-12-22	criteria provided, single submitter	clinical testing
GeneDx	RCV001538923	SCV001756642	benign	not provided	2020-12-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001538963	SCV001756685	benign	not provided	2018-06-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001538978	SCV001756701	benign	not provided	2018-08-16	criteria provided, single submitter	clinical testing
GeneDx	RCV001539000	SCV001756727	benign	not provided	2019-03-01	criteria provided, single submitter	clinical testing
GeneDx	RCV001539002	SCV001756729	likely benign	not provided	2018-07-30	criteria provided, single submitter	clinical testing
GeneDx	RCV001539044	SCV001756776	benign	not provided	2021-06-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001539047	SCV001756779	benign	not provided	2018-06-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001539082	SCV001756819	benign	not provided	2020-08-02	criteria provided, single submitter	clinical testing
GeneDx	RCV001539134	SCV001756878	benign	not provided	2021-05-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001539181	SCV001756925	likely benign	not provided	2018-07-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001539239	SCV001756986	benign	not provided	2018-06-16	criteria provided, single submitter	clinical testing
GeneDx	RCV001539328	SCV001757087	benign	not provided	2020-12-04	criteria provided, single submitter	clinical testing
GeneDx	RCV001539340	SCV001757102	benign	not provided	2019-06-21	criteria provided, single submitter	clinical testing
GeneDx	RCV001539382	SCV001757152	benign	not provided	2018-07-09	criteria provided, single submitter	clinical testing
GeneDx	RCV001539398	SCV001757172	benign	not provided	2018-07-17	criteria provided, single submitter	clinical testing
GeneDx	RCV001539443	SCV001757225	benign	not provided	2018-11-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001539489	SCV001757275	benign	not provided	2019-08-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001539490	SCV001757276	benign	not provided	2021-06-19	criteria provided, single submitter	clinical testing
GeneDx	RCV001539506	SCV001757293	benign	not provided	2018-11-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001539591	SCV001757379	benign	not provided	2019-08-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001539692	SCV001757492	benign	not provided	2018-07-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001539716	SCV001757519	likely benign	not provided	2019-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001539837	SCV001757656	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
GeneDx	RCV001539896	SCV001757720	benign	not provided	2021-04-25	criteria provided, single submitter	clinical testing
GeneDx	RCV001539918	SCV001757743	benign	not provided	2021-05-17	criteria provided, single submitter	clinical testing
GeneDx	RCV001539951	SCV001757779	benign	not provided	2018-07-06	criteria provided, single submitter	clinical testing
GeneDx	RCV001539988	SCV001757818	benign	not provided	2018-07-03	criteria provided, single submitter	clinical testing
GeneDx	RCV001540039	SCV001757875	likely benign	not provided	2019-01-13	criteria provided, single submitter	clinical testing
GeneDx	RCV001540129	SCV001757975	benign	not provided	2018-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001540155	SCV001758007	benign	not provided	2018-06-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001540181	SCV001758036	benign	not provided	2018-10-17	criteria provided, single submitter	clinical testing
GeneDx	RCV001540294	SCV001758166	benign	not provided	2018-07-05	criteria provided, single submitter	clinical testing
GeneDx	RCV001540477	SCV001758368	benign	not provided	2018-06-23	criteria provided, single submitter	clinical testing
GeneDx	RCV001540538	SCV001758432	benign	not provided	2021-06-19	criteria provided, single submitter	clinical testing
GeneDx	RCV001540549	SCV001758444	likely benign	not provided	2018-09-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001540617	SCV001758519	benign	not provided	2018-06-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001540772	SCV001758693	benign	not provided	2021-06-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001540860	SCV001758788	benign	not provided	2021-05-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001541076	SCV001759031	likely benign	not provided	2019-06-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001541088	SCV001759043	benign	not provided	2018-06-23	criteria provided, single submitter	clinical testing
GeneDx	RCV001541090	SCV001759046	benign	not provided	2018-07-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001541203	SCV001759172	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
GeneDx	RCV001541222	SCV001759194	benign	not provided	2021-05-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001541328	SCV001759308	benign	not provided	2018-11-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001541387	SCV001759380	likely benign	not provided	2018-11-16	criteria provided, single submitter	clinical testing
GeneDx	RCV001541412	SCV001759409	benign	not provided	2018-08-30	criteria provided, single submitter	clinical testing
GeneDx	RCV001541551	SCV001759565	likely benign	not provided	2018-07-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001541563	SCV001759580	likely benign	not provided	2019-08-20	criteria provided, single submitter	clinical testing
GeneDx	RCV001541604	SCV001759623	benign	not provided	2018-06-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001541634	SCV001759656	benign	not provided	2021-05-24	criteria provided, single submitter	clinical testing
GeneDx	RCV001541652	SCV001759677	benign	not provided	2021-06-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001541671	SCV001759697	benign	not provided	2018-11-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001541697	SCV001759725	benign	not provided	2018-06-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001541849	SCV001759888	likely benign	not provided	2018-06-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001541855	SCV001759896	likely benign	not provided	2020-03-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001541875	SCV001759921	benign	not provided	2018-11-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001541888	SCV001759955	benign	not provided	2021-06-18	criteria provided, single submitter	clinical testing
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	RCV001542276	SCV001760959	uncertain significance	not provided	2020-06-12	criteria provided, single submitter	clinical testing	The maternally inherited Xq21.1 duplication is a 323KB tandem duplication on the long arm of the X chromosome. This duplication contains 4 OMIM associated genes including full duplication of TAF9B and PGK1, as well as partial duplication of genes CYSLTR1 and ATP7A. To our current knowledge, the duplication identified in this individual has not been reported in the literature. Of the four OMIM associated genes within this duplication, two are disease associated. Pathogenic variants in PGK1 are associated with Phosphoglycerate kinase 1 deficiency (MIM#300653), and pathogenic variants in ATP7A are associated with Menkes disease (MIM#309400), Occipital horn syndrome (MIM#304150), and Spinal muscular atrophy, distal, X-Linked 3 (MIM#300489). Given the uncertainty regarding the functional consequence of the Xq21.1 duplication, it is reported here as a Variant of Uncertain Significance.
New York Genome Center	RCV001542282	SCV001760965	uncertain significance	not provided	2020-05-29	criteria provided, single submitter	clinical testing
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	RCV001542300	SCV001760985	uncertain significance	not provided	2020-07-03	criteria provided, single submitter	clinical testing
New York Genome Center	RCV001542301	SCV001760986	uncertain significance	not provided	2020-07-03	criteria provided, single submitter	clinical testing	The inherited 16p11.2 duplication identified in this individual is a 223.3KB duplication on the short arm of chromosome 16. 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 common, recurrent 16p11.2 duplication syndrome is a ~550KB recurrent copy number gain between BP4-BP5 [MIM#614671] [PMID:18184952; PMID:26629640]. The duplication identified here is an atypical distal duplication of 16p between BP2 and BP3, and contains OMIM associated genes ATXN2L, TUFM, SH2B1, ATP2A1, RABEP2, CD19, NFATC2IP, SPNS1, and LAT. Four of these genes are associated with autosomal recessive phenotypes including TUFM (AR Combined oxidative phosphorylation deficiency 4; MIM#610678), ATP2A1 (AR Brody Myopathy; MIM#601003), CD19 (AR Immunodeficiency, common variable 3;MIM#613493), and LAT (AR Immunodeficiency 52; MIM#617514). Similar duplications containing the same OMIM genes have been reported in ClinVar as Pathogenic (VarID:395931, 396629). The BP2-BP3 duplication has been identified in individuals with developmental delay, intellectual disability, and autism [PMID:27240531; PMID:32537635; PMID:30283035; PMID:21841781; PMID:19914906; PMID:19755429], although 16p11.2 distal duplications have also been observed in healthy asymptomatic individuals [PMID:27240531; PMID:30283035; PMID:19914906]. Phenotypic variability is also observed, and individuals with 16p11.2 distal duplications have been reported with additional heterogenous phenotypes including dysmorphic features, cleft lip/palate, scoliosis, and ocular findings [PMID:27240531; PMID:32537635; PMID:30283035; PMID:21841781; PMID:19914906; PMID:19755429]. Sonderby et. al [PMID:30283035] also found a correlation between individuals with the 16p11.2 distal duplication and decreased brain volume in specific regions, although additional studies are needed to confirm this finding. The inherited 16p11.2 duplication identified here is reported as a Variant of Uncertain Significance.
New York Genome Center	RCV001542310	SCV001760995	uncertain significance	not provided	2020-07-10	criteria provided, single submitter	clinical testing
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	RCV001542377	SCV001761070	uncertain significance	not provided	2020-05-29	criteria provided, single submitter	clinical testing
New York Genome Center	RCV001542382	SCV001761077	likely pathogenic	Galactosylceramide beta-galactosidase deficiency	2020-07-03	criteria provided, single submitter	clinical testing
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.
New York Genome Center	RCV001542403	SCV001761102	uncertain significance	Intellectual disability, X-linked 21	2020-07-17	criteria provided, single submitter	clinical testing
New York Genome Center	RCV001542404	SCV001761103	uncertain significance	Developmental and epileptic encephalopathy, 26	2020-07-03	criteria provided, single submitter	clinical testing	The inherited 20q13.13 duplication is a 197.7Kb tandem duplication on the long arm of chromosome 20 thta contains four OMIM associated protein-coding genes including full duplication of DDX27 and ZNFX1, as well as partial duplication of STAU1 and KCNB1. To our current knowledge, the duplication identified in this individual has not been reported in affected individuals the literature. Of the four OMIM associated protein-coding genes within this duplication, only KCNB1is disease associated. KCNB1gene consists of a total of two exons that encode a protein of 858 amino acids. This duplication contains exon 2 (but not exon 1) of the KCNB1 gene. The ClinVar database contains a 366.9 kb duplication that involves the exon 2 of KCNB1 (i.e. partial duplication of KCNB1, ClinVar variation ID:146041), and is classified as a variant of uncertain significance. The exact duplication identified in this individual has not been reported in the literature. Given the uncertainty regarding the functional consequencesof the inherited 20q13.13 duplication it is reported as a Variant of Uncertain Significance.
New York Genome Center	RCV001542428	SCV001761130	uncertain significance	Kleefstra syndrome 2	2020-06-26	criteria provided, single submitter	clinical testing	The inherited 349 kb duplication results in duplication of the first 38 exons (of 59) of the KMT2C gene. The majority of pathogenic variants in KMT2C are nonsense or frameshift [3,4], suggesting loss-of-function is the likely mechanism of disease. Moreover, ClinGen Dosage Sensitivity curation [5] indicates that the KMT2C gene has haploinsufficiency score of 3 (i.e. sufficient evidence for haploinsufficiency) whereas triplosensitivity score is zero (i.e., no evidence for triplosensitivity). There are no additional protein coding genes located within this duplication. Based on the available evidence, the 349 kb duplication inherited from an asymptomatic parent is assessed as a variant of uncertain significance.
New York Genome Center	RCV001542429	SCV001761131	uncertain significance	not provided	2020-06-26	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001543588	SCV001762260	likely pathogenic	not provided	2021-06-17	criteria provided, single submitter	clinical testing
GeneDx	RCV001544701	SCV001763879	likely benign	not provided	2019-07-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001544765	SCV001763961	likely benign	not provided	2018-09-16	criteria provided, single submitter	clinical testing
GeneDx	RCV001544792	SCV001763991	likely benign	not provided	2019-06-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001544915	SCV001764139	likely benign	not provided	2019-08-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001544930	SCV001764158	likely benign	not provided	2018-12-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001544952	SCV001764183	likely benign	not provided	2018-07-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001544961	SCV001764193	likely benign	not provided	2019-08-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001544965	SCV001764197	likely benign	not provided	2021-01-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001545111	SCV001764375	likely benign	not provided	2019-09-13	criteria provided, single submitter	clinical testing
GeneDx	RCV001545124	SCV001764393	likely benign	not provided	2018-07-06	criteria provided, single submitter	clinical testing
GeneDx	RCV001545174	SCV001764452	likely benign	not provided	2018-07-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001545245	SCV001764537	likely benign	not provided	2018-07-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001545287	SCV001764593	likely benign	not provided	2019-09-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001545302	SCV001764612	likely benign	not provided	2018-10-24	criteria provided, single submitter	clinical testing
GeneDx	RCV001545313	SCV001764624	likely benign	not provided	2018-09-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001545319	SCV001764633	likely benign	not provided	2019-12-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001545500	SCV001764842	likely benign	not provided	2018-09-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001545649	SCV001765025	likely benign	not provided	2019-06-17	criteria provided, single submitter	clinical testing
GeneDx	RCV001545659	SCV001765036	likely benign	not provided	2018-08-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001545667	SCV001765045	likely benign	not provided	2018-07-06	criteria provided, single submitter	clinical testing
GeneDx	RCV001545923	SCV001765345	likely benign	not provided	2018-07-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001546017	SCV001765457	likely benign	not provided	2019-08-21	criteria provided, single submitter	clinical testing
GeneDx	RCV001546105	SCV001765561	likely benign	not provided	2019-02-24	criteria provided, single submitter	clinical testing
GeneDx	RCV001546195	SCV001765671	likely benign	not provided	2018-07-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001546200	SCV001765678	likely benign	not provided	2018-07-09	criteria provided, single submitter	clinical testing
GeneDx	RCV001546330	SCV001765826	likely benign	not provided	2018-07-09	criteria provided, single submitter	clinical testing
GeneDx	RCV001546341	SCV001765838	likely benign	not provided	2019-08-21	criteria provided, single submitter	clinical testing
GeneDx	RCV001546401	SCV001765911	likely benign	not provided	2019-09-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001546440	SCV001765958	likely benign	not provided	2019-08-16	criteria provided, single submitter	clinical testing
GeneDx	RCV001546445	SCV001765965	likely benign	not provided	2019-09-06	criteria provided, single submitter	clinical testing
GeneDx	RCV001546488	SCV001766015	likely benign	not provided	2018-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001546545	SCV001766077	likely benign	not provided	2018-07-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001546549	SCV001766081	likely benign	not provided	2018-08-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001546650	SCV001766202	likely benign	not provided	2018-06-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001546725	SCV001766296	likely benign	not provided	2018-08-03	criteria provided, single submitter	clinical testing
GeneDx	RCV001546739	SCV001766314	likely benign	not provided	2018-07-09	criteria provided, single submitter	clinical testing
GeneDx	RCV001546757	SCV001766335	likely benign	not provided	2018-10-17	criteria provided, single submitter	clinical testing
GeneDx	RCV001546772	SCV001766352	likely benign	not provided	2019-08-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001546798	SCV001766382	likely benign	not provided	2018-11-16	criteria provided, single submitter	clinical testing
GeneDx	RCV001546864	SCV001766461	likely benign	not provided	2018-10-02	criteria provided, single submitter	clinical testing
GeneDx	RCV001546871	SCV001766468	likely benign	not provided	2018-06-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001546977	SCV001766593	likely benign	not provided	2018-08-03	criteria provided, single submitter	clinical testing
GeneDx	RCV001547035	SCV001766654	likely benign	not provided	2018-07-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001547063	SCV001766685	likely benign	not provided	2018-08-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001547121	SCV001766751	likely benign	not provided	2019-11-04	criteria provided, single submitter	clinical testing
GeneDx	RCV001547191	SCV001766839	likely benign	not provided	2018-06-22	criteria provided, single submitter	clinical testing
GeneDx	RCV001547206	SCV001766856	likely benign	not provided	2019-07-05	criteria provided, single submitter	clinical testing
GeneDx	RCV001547274	SCV001766938	likely benign	not provided	2018-11-16	criteria provided, single submitter	clinical testing
GeneDx	RCV001547302	SCV001766971	likely benign	not provided	2018-08-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001547322	SCV001766994	likely benign	not provided	2018-06-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001547352	SCV001767037	likely benign	not provided	2018-09-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001547363	SCV001767050	likely benign	not provided	2018-07-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001547368	SCV001767056	likely benign	not provided	2019-08-13	criteria provided, single submitter	clinical testing
GeneDx	RCV001547390	SCV001767083	likely benign	not provided	2019-05-20	criteria provided, single submitter	clinical testing
GeneDx	RCV001547525	SCV001767257	likely benign	not provided	2018-07-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001547622	SCV001767373	likely benign	not provided	2018-07-06	criteria provided, single submitter	clinical testing
GeneDx	RCV001547629	SCV001767382	likely benign	not provided	2018-07-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001547667	SCV001767429	likely benign	not provided	2019-10-30	criteria provided, single submitter	clinical testing
GeneDx	RCV001547860	SCV001767660	likely benign	not provided	2018-06-23	criteria provided, single submitter	clinical testing
GeneDx	RCV001547874	SCV001767676	likely benign	not provided	2018-07-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001547876	SCV001767682	uncertain significance	not provided	2019-07-05	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; No data available from control populations to assess the frequency of this variant
GeneDx	RCV001547879	SCV001767685	likely benign	not provided	2020-01-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001548003	SCV001767845	likely benign	not provided	2018-12-23	criteria provided, single submitter	clinical testing
GeneDx	RCV001548187	SCV001768054	likely benign	not provided	2018-07-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001548345	SCV001768240	likely benign	not provided	2018-10-27	criteria provided, single submitter	clinical testing
GeneDx	RCV001548381	SCV001768281	likely benign	not provided	2019-11-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001548386	SCV001768288	likely benign	not provided	2018-09-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001548425	SCV001768332	likely benign	not provided	2018-07-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001549312	SCV001769437	likely benign	not provided	2018-07-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001549347	SCV001769481	likely benign	not provided	2020-04-06	criteria provided, single submitter	clinical testing
GeneDx	RCV001549514	SCV001769679	likely benign	not provided	2019-02-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001549542	SCV001769719	likely benign	not provided	2018-06-21	criteria provided, single submitter	clinical testing
GeneDx	RCV001549556	SCV001769735	likely benign	not provided	2020-04-02	criteria provided, single submitter	clinical testing
GeneDx	RCV001549643	SCV001769828	likely benign	not provided	2019-08-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001549681	SCV001769875	likely benign	not provided	2019-05-19	criteria provided, single submitter	clinical testing
GeneDx	RCV001549798	SCV001770014	likely benign	not provided	2019-08-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001549842	SCV001770070	likely benign	not provided	2018-12-05	criteria provided, single submitter	clinical testing
GeneDx	RCV001549854	SCV001770082	likely benign	not provided	2019-01-20	criteria provided, single submitter	clinical testing
GeneDx	RCV001549970	SCV001770217	likely benign	not provided	2019-12-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001550034	SCV001770302	likely benign	not provided	2020-08-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001550037	SCV001770305	likely benign	not provided	2019-08-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001550060	SCV001770331	likely benign	not provided	2018-12-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001550099	SCV001770379	likely benign	not provided	2019-01-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001550190	SCV001770482	likely benign	not provided	2018-10-21	criteria provided, single submitter	clinical testing
GeneDx	RCV001550257	SCV001770557	likely benign	not provided	2019-08-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001550316	SCV001770626	likely benign	not provided	2020-05-30	criteria provided, single submitter	clinical testing
GeneDx	RCV001550375	SCV001770690	likely benign	not provided	2018-08-17	criteria provided, single submitter	clinical testing
GeneDx	RCV001550540	SCV001770879	likely benign	not provided	2018-09-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001550682	SCV001771052	likely benign	not provided	2020-03-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001550688	SCV001771061	likely benign	not provided	2018-08-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001550719	SCV001771097	likely benign	not provided	2018-07-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001550733	SCV001771113	likely benign	not provided	2018-07-02	criteria provided, single submitter	clinical testing
GeneDx	RCV001550756	SCV001771140	likely benign	not provided	2018-07-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001550780	SCV001771167	likely benign	not provided	2019-08-20	criteria provided, single submitter	clinical testing
GeneDx	RCV001550805	SCV001771195	likely benign	not provided	2019-10-21	criteria provided, single submitter	clinical testing
GeneDx	RCV001550810	SCV001771200	likely benign	not provided	2018-09-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001550840	SCV001771235	likely benign	not provided	2018-08-30	criteria provided, single submitter	clinical testing
GeneDx	RCV001550873	SCV001771272	likely benign	not provided	2020-03-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001550941	SCV001771349	likely benign	not provided	2018-07-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001551061	SCV001771486	likely benign	not provided	2019-02-24	criteria provided, single submitter	clinical testing
GeneDx	RCV001551068	SCV001771494	uncertain significance	not provided	2019-12-24	criteria provided, single submitter	clinical testing	Describes a nucleotide substitution 900 base pairs upstream of the ATG translational start site in the PTEN promoter region; Variants within the PTEN promoter have been observed in individuals with features of Cowden syndrome (Zhou 2003); Has not been previously published as pathogenic or benign to our knowledge; No data available from control populations to assess the frequency of this variant; Also known as c.-899C>G; This variant is associated with the following publications: (PMID: 12844284)
GeneDx	RCV001551124	SCV001771560	likely benign	not provided	2019-05-20	criteria provided, single submitter	clinical testing
GeneDx	RCV001551176	SCV001771629	likely benign	not provided	2018-07-09	criteria provided, single submitter	clinical testing
GeneDx	RCV001551177	SCV001771630	likely benign	not provided	2018-09-27	criteria provided, single submitter	clinical testing
GeneDx	RCV001551248	SCV001771715	likely benign	not provided	2018-07-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001551302	SCV001771781	likely benign	not provided	2019-08-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001551351	SCV001771837	likely benign	not provided	2018-08-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001551364	SCV001771853	likely benign	not provided	2019-09-20	criteria provided, single submitter	clinical testing
GeneDx	RCV001551403	SCV001771907	likely benign	not provided	2019-08-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001551489	SCV001772010	likely benign	not provided	2018-07-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001551498	SCV001772020	likely benign	not provided	2018-07-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001551531	SCV001772055	likely benign	not provided	2019-08-06	criteria provided, single submitter	clinical testing
GeneDx	RCV001551571	SCV001772102	likely benign	not provided	2019-08-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001551578	SCV001772112	likely benign	not provided	2018-08-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001551620	SCV001772161	likely benign	not provided	2019-05-03	criteria provided, single submitter	clinical testing
GeneDx	RCV001551679	SCV001772238	likely benign	not provided	2018-07-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001551766	SCV001772339	likely benign	not provided	2019-04-20	criteria provided, single submitter	clinical testing
GeneDx	RCV001551881	SCV001772478	likely benign	not provided	2019-10-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001551940	SCV001772548	likely benign	not provided	2018-07-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001552020	SCV001772634	likely benign	not provided	2018-06-19	criteria provided, single submitter	clinical testing
GeneDx	RCV001552046	SCV001772662	likely benign	not provided	2018-12-22	criteria provided, single submitter	clinical testing
GeneDx	RCV001552178	SCV001772825	likely benign	not provided	2019-08-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001552187	SCV001772835	likely benign	not provided	2019-12-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001552207	SCV001772857	likely benign	not provided	2018-06-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001552271	SCV001772929	likely benign	not provided	2019-11-02	criteria provided, single submitter	clinical testing
GeneDx	RCV001552359	SCV001773031	likely benign	not provided	2019-06-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001552397	SCV001773075	likely benign	not provided	2020-03-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001552417	SCV001773099	likely benign	not provided	2019-10-24	criteria provided, single submitter	clinical testing
GeneDx	RCV001552505	SCV001773203	likely benign	not provided	2018-08-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001552509	SCV001773208	likely benign	not provided	2018-08-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001552559	SCV001773265	likely benign	not provided	2020-02-13	criteria provided, single submitter	clinical testing
GeneDx	RCV001552659	SCV001773387	likely benign	not provided	2019-11-13	criteria provided, single submitter	clinical testing
GeneDx	RCV001552762	SCV001773512	likely benign	not provided	2019-04-16	criteria provided, single submitter	clinical testing
GeneDx	RCV001552823	SCV001773587	likely benign	not provided	2019-12-24	criteria provided, single submitter	clinical testing
GeneDx	RCV001552967	SCV001773751	likely benign	not provided	2018-06-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001552993	SCV001773784	likely benign	not provided	2018-08-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001553026	SCV001773821	likely benign	not provided	2020-08-04	criteria provided, single submitter	clinical testing
GeneDx	RCV001553161	SCV001773978	likely benign	not provided	2018-10-05	criteria provided, single submitter	clinical testing
GeneDx	RCV001553371	SCV001774230	likely benign	not provided	2021-01-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001553413	SCV001774275	likely benign	not provided	2018-09-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001553462	SCV001774335	likely benign	not provided	2019-08-24	criteria provided, single submitter	clinical testing
GeneDx	RCV001553506	SCV001774386	likely benign	not provided	2019-04-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001553531	SCV001774416	likely benign	not provided	2019-10-13	criteria provided, single submitter	clinical testing
GeneDx	RCV001554962	SCV001776303	likely benign	not provided	2018-07-09	criteria provided, single submitter	clinical testing
GeneDx	RCV001555015	SCV001776361	likely benign	not provided	2018-07-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001555034	SCV001776383	likely benign	not provided	2019-08-08	criteria provided, single submitter	clinical testing
GeneDx	RCV001555060	SCV001776413	likely benign	not provided	2018-11-08	criteria provided, single submitter	clinical testing
GeneDx	RCV001555063	SCV001776417	likely benign	not provided	2019-08-13	criteria provided, single submitter	clinical testing
GeneDx	RCV001555106	SCV001776460	likely benign	not provided	2018-08-17	criteria provided, single submitter	clinical testing
GeneDx	RCV001555173	SCV001776542	likely benign	not provided	2020-01-23	criteria provided, single submitter	clinical testing
GeneDx	RCV001555183	SCV001776554	likely benign	not provided	2019-08-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001555231	SCV001776611	likely benign	not provided	2018-06-30	criteria provided, single submitter	clinical testing
GeneDx	RCV001555310	SCV001776703	likely benign	not provided	2018-08-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001555360	SCV001776768	likely benign	not provided	2019-10-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001555513	SCV001776949	likely benign	not provided	2018-09-22	criteria provided, single submitter	clinical testing
GeneDx	RCV001555519	SCV001776957	likely benign	not provided	2018-07-11	criteria provided, single submitter	clinical testing
GeneDx	RCV001555633	SCV001777081	likely benign	not provided	2018-11-08	criteria provided, single submitter	clinical testing
GeneDx	RCV001555638	SCV001777086	likely benign	not provided	2018-10-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001555643	SCV001777092	likely benign	not provided	2018-08-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001555674	SCV001777126	likely benign	not provided	2018-08-03	criteria provided, single submitter	clinical testing
GeneDx	RCV001555757	SCV001777220	likely benign	not provided	2018-08-17	criteria provided, single submitter	clinical testing
GeneDx	RCV001555759	SCV001777222	likely benign	not provided	2019-08-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001555776	SCV001777243	uncertain significance	not provided	2021-06-23	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Located in a region that tolerates variation and lacks pathogenic variants; This variant is associated with the following publications: (PMID: 27535533)
GeneDx	RCV001555801	SCV001777270	likely benign	not provided	2019-04-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001555836	SCV001777312	likely benign	not provided	2019-09-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001555865	SCV001777350	likely benign	not provided	2018-07-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001555898	SCV001777388	likely benign	not provided	2018-10-24	criteria provided, single submitter	clinical testing
GeneDx	RCV001555929	SCV001777422	likely benign	not provided	2019-08-18	criteria provided, single submitter	clinical testing
GeneDx	RCV001556044	SCV001777556	likely benign	not provided	2019-04-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001556161	SCV001777691	likely benign	not provided	2018-10-17	criteria provided, single submitter	clinical testing
GeneDx	RCV001556195	SCV001777730	likely benign	not provided	2019-09-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001556299	SCV001777857	likely benign	not provided	2018-10-09	criteria provided, single submitter	clinical testing
GeneDx	RCV001556303	SCV001777861	likely benign	not provided	2018-10-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001556437	SCV001778019	likely benign	not provided	2018-07-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001556617	SCV001778230	likely benign	not provided	2018-07-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001556666	SCV001778287	uncertain significance	not provided	2020-08-21	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); Canonical splice site variant in a gene for which loss-of-function is not a known mechanism of disease; Has not been previously published as pathogenic or benign to our knowledge
GeneDx	RCV001556691	SCV001778318	likely benign	not provided	2018-07-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001556813	SCV001778460	likely benign	not provided	2019-10-12	criteria provided, single submitter	clinical testing
GeneDx	RCV001556867	SCV001778523	likely benign	not provided	2019-10-21	criteria provided, single submitter	clinical testing
GeneDx	RCV001556910	SCV001778575	likely benign	not provided	2018-09-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001557127	SCV001778831	likely benign	not provided	2019-07-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001557246	SCV001778973	likely benign	not provided	2019-10-31	criteria provided, single submitter	clinical testing
GeneDx	RCV001557254	SCV001778982	likely benign	not provided	2019-02-05	criteria provided, single submitter	clinical testing
GeneDx	RCV001557275	SCV001779006	likely benign	not provided	2019-10-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001557331	SCV001779078	likely benign	not provided	2018-11-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001557374	SCV001779127	likely benign	not provided	2018-12-23	criteria provided, single submitter	clinical testing
GeneDx	RCV001557494	SCV001779265	likely benign	not provided	2019-03-21	criteria provided, single submitter	clinical testing
GeneDx	RCV001557621	SCV001779413	likely benign	not provided	2018-06-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001557687	SCV001779494	likely benign	not provided	2018-07-07	criteria provided, single submitter	clinical testing
GeneDx	RCV001557996	SCV001779857	likely benign	not provided	2018-06-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001558046	SCV001779917	likely benign	not provided	2019-06-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001558158	SCV001780047	likely benign	not provided	2019-07-13	criteria provided, single submitter	clinical testing
GeneDx	RCV001558162	SCV001780051	likely benign	not provided	2018-06-26	criteria provided, single submitter	clinical testing
GeneDx	RCV001558168	SCV001780058	likely benign	not provided	2019-02-14	criteria provided, single submitter	clinical testing
GeneDx	RCV001558224	SCV001780125	likely benign	not provided	2019-06-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001558289	SCV001780203	likely benign	not provided	2019-09-23	criteria provided, single submitter	clinical testing