Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001766866 | SCV001989804 | uncertain significance | not provided | 2019-05-16 | 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 a deleterious effect |
Color Diagnostics, |
RCV003533019 | SCV004363098 | uncertain significance | Cardiomyopathy | 2022-11-21 | criteria provided, single submitter | clinical testing | This missense variant replaces asparagine with lysine at codon 413 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 not been reported in individuals affected with DSC2-related disorders in the literature. This variant has been identified in 1/31370 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. |
Invitae | RCV003771947 | SCV004633616 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2023-01-10 | criteria provided, single submitter | clinical testing | 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. 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 expected to disrupt DSC2 protein function. ClinVar contains an entry for this variant (Variation ID: 1305913). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. This variant is present in population databases (rs765511398, gnomAD 0.002%). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 413 of the DSC2 protein (p.Asn413Lys). |