Submissions for variant NM_001943.5(DSG2):c.473T>G (p.Val158Gly)

gnomAD frequency: 0.00550  dbSNP: rs191143292

Total submissions: 21

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000148470	SCV000051527	benign	Arrhythmogenic right ventricular cardiomyopathy	2013-06-24	criteria provided, single submitter	research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037307	SCV000060964	benign	not specified	2017-10-11	criteria provided, single submitter	clinical testing	p.Val158Gly in exon 5 of DSG2: This variant is not expected to have clinical sig nificance because it is not located within the splice consensus sequence and has been identified in 0.8% (212/25742) of Finnish chromosomes by the Genome Aggreg ation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs191143292). AC MG/AMP Criteria applied: BA1 (Richards 2015).
GeneDx	RCV000037307	SCV000168233	benign	not specified	2012-05-01	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.
CSER _CC_NCGL, University of Washington	RCV000211473	SCV000212209	likely benign	Arrhythmogenic right ventricular dysplasia 1	2015-03-11	criteria provided, single submitter	research
Eurofins Ntd Llc (ga)	RCV000037307	SCV000231023	likely benign	not specified	2015-03-18	criteria provided, single submitter	clinical testing
Invitae	RCV001081252	SCV000262068	benign	Arrhythmogenic right ventricular dysplasia 10	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000250164	SCV000318919	benign	Cardiovascular phenotype	2015-11-20	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589551	SCV000697889	benign	not provided	2016-01-26	criteria provided, single submitter	clinical testing	Variant summary: This c.473T>G variant affects a conserved nucleotide, resulting in amino acid change from Val to Gly. 3/4 in-silico tools predict this variant to be damaging; however, results from in silico prediction are not definitive. This variant was found in 674/124228 control chromosomes including the broad and large populations from ExAC at a frequency of 0.0054255, which is more than 216 times greater than the maximal expected frequency of a pathogenic allele (0.000025) in this gene, suggesting this variant is benign. In addition, three homozygotes have also been reported from the European (Non-Finnish) population from ExAC, further supporting its benign outcome for the dominant disorders associated with this gene. This variant has been reported in literature in many patients with varying cardiological phenotypes, namely ARVD, DCM, Brugada Syndrome, and Arrhythmia; however, without strong evidence for causality. Rather, this variant was reported to co-occur with DSG2 R46Q and PKP2 p.L452X, supporting for a benign outcome. The variant has also been reported in an unaffected relative of an ARVD family, suggesting a lack of cosegregation (Syrris_2007). Multiple clinical labs have classified this variant as benign/likely benign. Taken together, this variant has been classified as Benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000589551	SCV000883745	benign	not provided	2023-11-09	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000771099	SCV000902737	benign	Cardiomyopathy	2018-04-09	criteria provided, single submitter	clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000148470	SCV000987331	benign	Arrhythmogenic right ventricular cardiomyopathy		criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852740	SCV000995456	benign	Primary dilated cardiomyopathy; Cardiomyopathy	2019-06-11	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000589551	SCV002498359	likely benign	not provided	2024-05-01	criteria provided, single submitter	clinical testing	DSG2: BP4, BS2
Fulgent Genetics, Fulgent Genetics	RCV002490506	SCV002796082	likely benign	Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB	2022-04-22	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000148470	SCV004819447	benign	Arrhythmogenic right ventricular cardiomyopathy	2024-02-05	criteria provided, single submitter	clinical testing
CSER _CC_NCGL, University of Washington	RCV000148470	SCV000190170	likely benign	Arrhythmogenic right ventricular cardiomyopathy	2014-06-01	no assertion criteria provided	research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000589551	SCV001739838	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000037307	SCV001923770	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000037307	SCV001929204	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000037307	SCV001953280	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000037307	SCV001974892	benign	not specified		no assertion criteria provided	clinical testing