Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular 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, |
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. |