ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.799G>C (p.Ala267Pro)

dbSNP: rs966660258
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000607595 SCV000712045 uncertain significance not specified 2016-04-26 criteria provided, single submitter clinical testing The p.Ala267Pro variant in DSC2 has not been previously reported in individuals with cardiomyopathy and is absent from large population studies. Computational p rediction tools and conservation analysis suggest that this variant may impact t he protein, though this information is not predictive enough to determine pathog enicity. In summary, the clinical significance of the p.Ala267Pro variant is unc ertain.
Invitae RCV001300606 SCV001489752 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2022-07-26 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 267 of the DSC2 protein (p.Ala267Pro). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 27532257). ClinVar contains an entry for this variant (Variation ID: 504982). 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. 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.
Color Diagnostics, LLC DBA Color Health RCV003532186 SCV004363115 uncertain significance Cardiomyopathy 2023-04-17 criteria provided, single submitter clinical testing This missense variant replaces alanine with proline at codon 267 of the DSC2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in a dilated cardiomyopathy (PMID: 27532257). This variant has been identified in 1/251240 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.

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