Submissions for variant NM_001943.5(DSG2):c.1851C>T (p.Leu617=)

gnomAD frequency: 0.00017  dbSNP: rs202057770

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037274	SCV000060931	likely benign	not specified	2012-08-09	criteria provided, single submitter	clinical testing	Leu617Leu in exon 12 of DSG2: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 2/8470 European Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS/). Leu617Leu in exon 12 of DSG2 (allele frequ ency = 2/8740) **
Invitae	RCV000230544	SCV000287232	likely benign	Arrhythmogenic right ventricular dysplasia 10	2024-01-25	criteria provided, single submitter	clinical testing
GeneDx	RCV001701648	SCV000512864	likely benign	not provided	2021-04-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000619938	SCV000737548	likely benign	Cardiovascular phenotype	2016-05-26	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Color Diagnostics, LLC DBA Color Health	RCV000777968	SCV000914070	likely benign	Cardiomyopathy	2018-10-16	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000230544	SCV001282371	uncertain significance	Arrhythmogenic right ventricular dysplasia 10	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000777968	SCV001332951	benign	Cardiomyopathy	2017-12-21	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000037274	SCV001478649	likely benign	not specified	2021-01-28	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001701648	SCV004701880	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	DSG2: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV003904915	SCV004722834	likely benign	DSG2-related condition	2019-08-01	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Clinical Genetics, Academic Medical Center	RCV000037274	SCV001923749	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001701648	SCV001931028	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001701648	SCV001956568	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001701648	SCV001963916	likely benign	not provided		no assertion criteria provided	clinical testing