ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.1291A>G (p.Met431Val)

gnomAD frequency: 0.00006  dbSNP: rs377287621
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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 RCV001185846 SCV001352155 likely benign Cardiomyopathy 2018-12-19 criteria provided, single submitter clinical testing
Invitae RCV001876176 SCV002215759 uncertain significance Arrhythmogenic right ventricular dysplasia 11 2024-01-10 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 431 of the DSC2 protein (p.Met431Val). This variant is present in population databases (rs377287621, gnomAD 0.02%). 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: 924484). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt DSC2 protein function with a negative predictive value of 80%. 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.
Ambry Genetics RCV002379716 SCV002691373 likely benign Cardiovascular phenotype 2021-10-07 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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