Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001179315 | SCV001343946 | uncertain significance | Cardiomyopathy | 2023-06-21 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with asparagine at codon 640 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 been reported in an individual who experienced sudden cardiac death, who was diagnosed with arrhythmogenic cardiomyopathy at autopsy and determined to carry another pathogenic variant in the DSP gene (PMID: 31534214). This variant has been identified in 1/250566 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. |
Gene |
RCV001762169 | SCV001990666 | uncertain significance | not provided | 2019-03-28 | 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: 31534214) |
Invitae | RCV001854265 | SCV002180063 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2021-12-25 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 640 of the DSC2 protein (p.Asp640Asn). This variant is present in population databases (rs267605146, gnomAD 0.0009%). This missense change has been observed in individual(s) with arrhythmogenic cardiomyopathy on autopsy (PMID: 31534214). ClinVar contains an entry for this variant (Variation ID: 80797). 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: "Probably Damaging"; 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. |