ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1520G>A (p.Cys507Tyr) (rs121913009)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Health, Inc RCV001178344 SCV001342755 uncertain significance Cardiomyopathy 2019-09-23 criteria provided, single submitter clinical testing
Invitae RCV000018306 SCV001395117 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 10 2019-05-12 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 507 of the DSG2 protein (p.Cys507Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with arrhythmogenic right ventricular cardiomyopathy, including at least one individual with a second variant in the PKP2 gene (PMID: 20031617, 20152563). ClinVar contains an entry for this variant (Variation ID: 16813). 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 and their clinical significance is uncertain. 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.
GeneDx RCV001588816 SCV001824069 uncertain significance not provided 2019-08-08 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 32665702, 31402444, 31737537, 23871885, 23671136, 20031617, 20857253, 20152563, 16773573)
OMIM RCV000018306 SCV000038585 pathogenic Arrhythmogenic right ventricular cardiomyopathy, type 10 2006-07-01 no assertion criteria provided literature only

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