ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.874C>T (p.Arg292Cys) (rs770921270)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000545942 SCV000641996 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 10 2020-10-12 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 292 of the DSG2 protein (p.Arg292Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs770921270, ExAC 0.01%). This variant has ben reported in several individuals affected with arrhythmogenic right ventricular dysplasia, including in the homozygous state (PMID: 21606396, 22000064, 27532257, 22214898, 25820315, 29178656, 30454721). ClinVar contains an entry for this variant (Variation ID: 466351). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000845455 SCV000987544 uncertain significance Arrhythmogenic right ventricular cardiomyopathy criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000996666 SCV001151512 uncertain significance not provided 2017-03-01 criteria provided, single submitter clinical testing
Color Health, Inc RCV001180821 SCV001345845 uncertain significance Cardiomyopathy 2019-08-23 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000545942 SCV001369731 likely pathogenic Arrhythmogenic right ventricular cardiomyopathy, type 10 2020-03-13 criteria provided, single submitter clinical testing This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS4_Mod,PM2,PP3,PP4. This variant was detected in homozygous state.
Mayo Clinic Laboratories, Mayo Clinic RCV000996666 SCV001712935 uncertain significance not provided 2020-02-27 criteria provided, single submitter clinical testing
GeneDx RCV000996666 SCV001789066 uncertain significance not provided 2021-04-02 no assertion criteria provided clinical testing 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: 30454721, 21606396, 28097316, 25820315, 22000064, 22214898, 27532257, 29178656)

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