ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.2759T>G (p.Val920Gly) (rs142841727)

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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000148473 SCV000051528 benign Arrhythmogenic right ventricular cardiomyopathy 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037294 SCV000060951 likely benign not specified 2015-08-21 criteria provided, single submitter clinical testing p.Val920Gly in exon 15 of DSG2: This variant has been reported in several indivi duals with ARVC or DCM but did not segregate with disease in one family member ( Syrris 2007, Posch 2008, Barahona-Dussault 2010, Christensen 2010). It has been identified in 0.5% (316/66608) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs142841727). This freq uency strongly argues against a disease causing role but is too low to establish this with confidence.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000037294 SCV000226263 benign not specified 2015-05-04 criteria provided, single submitter clinical testing
GeneDx RCV000037294 SCV000233469 benign not specified 2015-05-08 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.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia RCV000148473 SCV000257908 benign Arrhythmogenic right ventricular cardiomyopathy 2015-06-19 criteria provided, single submitter clinical testing
Invitae RCV000755252 SCV000287237 benign Arrhythmogenic right ventricular cardiomyopathy, type 10 2020-12-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000245262 SCV000318981 benign Cardiovascular phenotype 2017-02-08 criteria provided, single submitter clinical testing Does not segregate with disease in family study (genes with incomplete penetrance);General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance;In silico models in agreement (benign);Subpopulation frequency in support of benign classification
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282261 SCV000603385 benign none provided 2020-04-09 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000037294 SCV000747997 benign not specified 2017-02-23 criteria provided, single submitter clinical testing
Color Health, Inc RCV000776064 SCV000910712 benign Cardiomyopathy 2018-04-08 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852745 SCV000995462 benign Arrhythmogenic right ventricular cardiomyopathy; Cardiomyopathy 2018-05-02 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000755252 SCV001287045 likely benign Arrhythmogenic right ventricular cardiomyopathy, type 10 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
CSER _CC_NCGL, University of Washington RCV000148473 SCV000190174 uncertain significance Arrhythmogenic right ventricular cardiomyopathy 2014-06-01 no assertion criteria provided research
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000037294 SCV000280084 uncertain significance not specified 2015-06-24 no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. We consider this variant to be of uncertain significance, likely benign, given it is present in multiple control samples and that it failed to segregate with disease in one family. This variant has been reported in 6 unrelated cases with either ARVC or DCM and as many as 6 total cases. Syrris et al (2006) initially identified the variant in a 17 yo male who had a sudden cardiac arrest, a left ventricular variant of ARVC was confirmed on autopsy. The proband’s father who had a positive phenotype on MRI and an abnormal signal average ECG was found to be genotype positive for the variant. Posch et al (2008) identified the variant in two families with dilated cardiomyopathy (note they refer to the variant as p.Val919Gly due to a numbering difference). However they report that the variant did not segregate with the phenotype in one family. In that family five affected relatives had the variant but one affected relative did not, indicating that it is likely not the primary causative variant of their disease. Christensen et al (2010) also reported the variant in 1 case that was clinically borderline for ARVC. Quarta et al (2011) found p.Val920Gly in 2 out of 100 families with ARVC. This is a conservative amino acid change with a nonpolar Valine replaced by a nonpolar Glyceine. SIFT predicts the amino acid change to be tolerated while PolyPhen predicts it to be probably damaging to the resulting protein. A variant in a nearby codon (p.Pro925Ser) has been reported in association with disease (University Medical Center Groningen ARVD/C Genetic Variants Database). Syrris et al (2006) reported that the variant was absent in 200 presumably healthy controls. Posch et al (2008) identified p.Val920Gly in 2 out of 432 presumably healthy control individuals. Christensen et al (2010) reported that the variant was present in 3 out of 650 individuals from a control population. Cox et al (2011) reported that the variant was absent in 200 controls. The variant is listed in dbSNP (rs142841727) with frequency data from the ClinSeq project, where it was seen in 8 of 660 individuals. It is listed in 1000Genomes, but only in reference to the dbSNP entry (as of April 17th, 2013). Additionally the variant was found in 41/4135 Caucasians and 6/1948 African American individuals in the NHLBI Exome Sequencing Project dataset (as of April 17th, 2013).
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000037294 SCV001740980 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001701728 SCV001930813 likely benign not provided no assertion criteria provided clinical testing

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