Submissions for variant NM_024422.6(DSC2):c.2498G>A (p.Arg833His)

gnomAD frequency: 0.00061  dbSNP: rs370325533

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000039425	SCV000063109	uncertain significance	not specified	2012-04-11	criteria provided, single submitter	clinical testing	The Arg833His variant (DSC2) has been identified in 3/3738 African American chro mosomes from a broad population by the NHLBI Exome Sequencing Project (http://ev s.gs.washington.edu/EVS) as well as in 1 of 854 control chromosomes (Kapplinger 2011). Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional information is needed to fully assess the clin ical significance of the Arg833His variant.
GeneDx	RCV000766860	SCV000233444	uncertain significance	not provided	2023-08-24	criteria provided, single submitter	clinical testing	Has been reported in association with HCM (Lopes et al., 2015) but has also been identified in healthy control cohorts (Kapplinger et al., 2011); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21636032, 25351510)
Invitae	RCV000229598	SCV000290732	likely benign	Arrhythmogenic right ventricular dysplasia 11	2024-01-06	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000244558	SCV000320492	likely benign	Cardiovascular phenotype	2019-02-28	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.
Fulgent Genetics, Fulgent Genetics	RCV000229598	SCV000611473	uncertain significance	Arrhythmogenic right ventricular dysplasia 11	2017-05-23	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001175843	SCV001339619	likely benign	Cardiomyopathy	2018-11-04	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000766860	SCV001923686	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000766860	SCV001930857	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000766860	SCV001970916	likely benign	not provided		no assertion criteria provided	clinical testing