ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1281A>T (p.Arg427Ser) (rs370547219)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000487007 SCV000567828 uncertain significance not provided 2017-04-18 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the DSG2 gene. The R427S variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R427S variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, this substitution occurs at a position that is not conserved across species.
Color Health, Inc RCV001176568 SCV001340588 uncertain significance Cardiomyopathy 2020-01-16 criteria provided, single submitter clinical testing
Invitae RCV001204581 SCV001375794 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 10 2020-10-26 criteria provided, single submitter clinical testing This sequence change replaces arginine with serine at codon 427 of the DSG2 protein (p.Arg427Ser). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and serine. This variant is present in population databases (rs370547219, ExAC 0.006%). This variant has not been reported in the literature in individuals with DSG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 419778). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). 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.

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