ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.2398G>T (p.Ala800Ser)

dbSNP: rs565136635
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Total submissions: 4
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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 RCV000156917 SCV000206638 uncertain significance not specified 2014-12-04 criteria provided, single submitter clinical testing The p.Ala800Ser variant in DSC2 has not been previously reported in individuals with cardiomyopathy or in large population studies. Alanine (Ala) at position 80 0 is not well conserved in evolution, raising the possibility that this change m ay be tolerated. Computational prediction tools also suggest that the p.Ala800Se r variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p .Ala800Ser variant is uncertain.
Illumina Laboratory Services, Illumina RCV001123910 SCV001282797 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV001123910 SCV001536217 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 800 of the DSC2 protein (p.Ala800Ser). The alanine residue is weakly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs565136635, ExAC 0.06%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 180113). 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: "Tolerated"; PolyPhen-2: "Not Available"; 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.
Color Diagnostics, LLC DBA Color Health RCV001525548 SCV001735693 likely benign Cardiomyopathy 2020-12-22 criteria provided, single submitter clinical testing

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