ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.1581C>G (p.Ile527Met)

gnomAD frequency: 0.00001  dbSNP: rs750329563
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001191872 SCV001359789 uncertain significance Cardiomyopathy 2023-01-10 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with methionine at codon 527 of the DSC2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 3/251158 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV001773445 SCV001993004 uncertain significance not provided 2019-07-01 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; 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 that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31983221)
Invitae RCV002559205 SCV003255028 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2022-07-19 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 928170). 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. 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: "Probably Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 31983221). This variant is present in population databases (rs750329563, gnomAD 0.006%). This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 527 of the DSC2 protein (p.Ile527Met).

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