Submissions for variant Multiple alleles

Total submissions: 28

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000170538	SCV000223133	pathogenic	Choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome	2014-12-02	criteria provided, single submitter	research
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000170540	SCV000223135	pathogenic	Choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome	2014-12-02	criteria provided, single submitter	research
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000170541	SCV000223136	pathogenic	Choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome	2014-12-02	criteria provided, single submitter	research
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000170542	SCV000223137	pathogenic	Choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome	2014-12-02	criteria provided, single submitter	research
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000170543	SCV000223138	pathogenic	Choanal atresia-hearing loss-cardiac defects-craniofacial dysmorphism syndrome	2014-12-02	criteria provided, single submitter	research
Neurogenetics Research Program, University of Adelaide	RCV001796558	SCV001737589	likely pathogenic	Cerebral palsy	2021-06-10	criteria provided, single submitter	research
Genomic Diagnostics Laboratory, National Institute of Medical Genomics	RCV001647442	SCV001761655	pathogenic	ALG1-congenital disorder of glycosylation	2021-07-23	criteria provided, single submitter	research	This variant in ALG1 gene has been never reported , and was absent from large population studies. Additionally, an in vitro functional study performed by our group indicate that it retaines the intron 1. In summary, this variant meets ACMG criteria to be classified as pathogenic .
Unidade de Genética Molecular, Centro Hospitalar Universitário do Porto	RCV002236175	SCV002014676	pathogenic	Becker muscular dystrophy		criteria provided, single submitter	clinical testing	A ~8Mb genomic inversion involving DMD intron 74 and a region located upstream of the PRDX4 gene was detected by Whole genome sequencing in a patient with Becker Muscular Dystrophy. Muscle mRNA analysis confirmed the presence of aberrant transcripts.
CFTR-France	RCV002284246	SCV002573607	pathogenic	Cystic fibrosis	2018-01-29	criteria provided, single submitter	curation
Institute of Human Genetics, University of Leipzig Medical Center	RCV002284571	SCV002573932	pathogenic	Cystic fibrosis	2022-09-05	criteria provided, single submitter	curation	This variant was identified in 1 patient with a clinically confirmed diagnosis of cystic fibrosis. The variant was classified in the context of a project re-classifying variants in the German Cystic Fibrosis Registry (Muko.e.V.). Link: https://www.muko.info/angebote/qualitaetsmanagement/register/cf-einrichtungen/mukoweb. Criteria applied: PVS1, PM2_SUP, PM3_STR, PP4 This variant has previously been described in the literature as: c.(164+1_165-1)_(1584+1_1585-1)del(2619+1_2620-1) or CFTRdele3-10,14b-16
Clinical Biochemistry Laboratory, Health Services Laboratory	RCV003447385	SCV004174335	pathogenic	Primary hyperoxaluria, type II	2023-10-27	criteria provided, single submitter	clinical testing	ACMG:PVS1 PS3 PM2 PM3 PP4
OMIM	RCV000000279	SCV000020423	pathogenic	Xeroderma pigmentosum, group C	1993-12-01	no assertion criteria provided	literature only
OMIM	RCV001799584	SCV000021227	risk factor	Myocardial infarction, susceptibility to	2006-01-01	no assertion criteria provided	literature only
OMIM	RCV000011206	SCV000031433	pathogenic	X-linked Alport syndrome	2019-01-31	no assertion criteria provided	literature only
OMIM	RCV000014500	SCV000034751	risk factor	Coronary heart disease, susceptibility to, 7	2004-10-01	no assertion criteria provided	literature only
OMIM	RCV004720230	SCV000035692	uncertain significance	not specified	2005-10-01	no assertion criteria provided	literature only
OMIM	RCV000015532	SCV000035797	benign	APOLIPOPROTEIN(a), TYPE C POLYMORPHISM	2020-08-07	no assertion criteria provided	literature only
OMIM	RCV000015533	SCV000035798	benign	APOLIPOPROTEIN(a), TYPE D POLYMORPHISM	2020-08-07	no assertion criteria provided	literature only
OMIM	RCV000016022	SCV000036289	pathogenic	Guttmacher syndrome	2002-05-01	no assertion criteria provided	literature only
OMIM	RCV000022537	SCV000043826	risk factor	Pregnancy loss, recurrent, susceptibility to, 3	2007-03-01	no assertion criteria provided	literature only
Clinical Biochemistry Laboratory, Health Services Laboratory	RCV000186455	SCV000239812	pathogenic	Primary hyperoxaluria, type II	2014-11-27	no assertion criteria provided	research
Laboratory of Gastroenterology and Hepatology, Radboud University Medical Center	RCV000239375	SCV000257477	pathogenic	Congenital disorders of glycosylation type II		no assertion criteria provided	research
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	RCV000495844	SCV000581393	likely pathogenic	Autosomal recessive nonsyndromic hearing loss 63	2016-08-31	no assertion criteria provided	clinical testing	MYH9 gene: The mutation c.922G>A (p.V308I) in exon 9 of MYH9 gene is reported in 1000 genome (0.04%) and ExAc (0.01%) databases and it is found to be pathogenic by Mutation Taster2, SIFT, Polyphen2 and LRT. The dbSNP number of this mutation is rs577429531. LRTOMT gene: The variant c.613_614insAGCT in exon 9 of LRTOMT gene is not reported in 1000 Genome and ExAC databases and it is found to be damaging by Mutation Taster2. The dbSNP number of this mutation is rs797044907. The proband, born of a non-consanguineous marriage, presented with clinical indication of dysplastic semicircular canals. She was diagnosed with bilateral incomplete cochlear partition. Upon further investigation her father was found to be heterozygous for c.922G>A (p.V308 I) mutation in MYH9 gene and her mother was found to be heterozygous for c.613_614insAGCT (p.S207AfsTer 38) variant in LRTOMT gene. During subsequent pregnancy, the CVS sample of mother is found to be heterozygous for c.922G>A (p.V308I) variant in MYH9 gene.
Center for Statistical Genetics, Columbia University	RCV000655893	SCV000608345	pathogenic	Hearing loss, autosomal recessive	2017-10-26	no assertion criteria provided	research	Digenic inheritance
Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas	RCV001171633	SCV000999906	affects	Rheumatoid arthritis	2019-11-30	no assertion criteria provided	research	Using four independent cohorts of arthritic patients, we identified an inverse correlation between SOCS1 mRNA expression and disease activity. Lower baseline SOCS1 levels were associated with poorer disease control. In vitro expression assays indicated that the minor allele of rs4780355 correlated with reduced SOCS1 expression, supporting a functional relationship between this SNP and disease progression, but only when the microsatellite 3x(TTTTC) is cis-acting.
Servicio de Hematología y Oncología médica, Universidad de Murcia	RCV001779980	SCV002016218	pathogenic	Hereditary antithrombin deficiency		no assertion criteria provided	research	AntiFXa 54%; Ag 41%
Undiagnosed Diseases Network, NIH	RCV002509904	SCV002818563	pathogenic	SSR4-congenital disorder of glycosylation	2022-03-15	no assertion criteria provided	clinical testing	It showed that there is a deletion which involves IDH3G, PLXNB3, SRPK3, SSR4, and HG38. This is on chromosome X and is described as G (153757278_153757299DEL; 153757300_153778281INV; 153778282_153795224DEL). This is a de novo variant which is associated with Congenital Disorder of Glycosylation type 1Y.
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV004586480	SCV005073730	affects	PAIN SENSITIVITY QUANTITATIVE TRAIT LOCUS 1		no assertion criteria provided	literature only	The paper by Habib et al., 2019 (PubMed 30929760) describes "a new human genetic disorder in a patient with hypoalgesia, altered fear and memory symptoms, and a non-anxious disposition is attributable to co-inheritance of a microdeletion in a novel pseudogene and a known FAAH hypomorphic SNP." The mechanism was not established but one hypothesis is that "the FAAH-OUT transcript normally functions as a decoy for microRNAs as a result of the high sequence homology, and protects FAAH mRNA from degradation."