ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.908C>T (p.Ser303Phe) (rs757792714)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000477384 SCV000551010 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 10 2016-06-28 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 303 of the DSG2 protein (p.Ser303Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is present in population databases (rs757792714, ExAC 0.001%) but has not been reported in the literature in individuals with a DSG2-related disease. 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, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Health, Inc RCV001186045 SCV001352383 uncertain significance Cardiomyopathy 2018-11-30 criteria provided, single submitter clinical testing
GeneDx RCV001550730 SCV001771110 uncertain significance not provided 2020-12-16 criteria provided, single submitter clinical testing Identified in one individual with arrhythmogenic right ventricular cardiomyopathy (ARVC) in published literature (Walsh et al., 2017); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in ClinVar but additional evidence is not available (ClinVar Variant ID#410368; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 31402444, 27532257)

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