Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001192239 | SCV001360266 | uncertain significance | Cardiomyopathy | 2024-01-10 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with alanine at codon 49 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 2/251350 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 | RCV003517316 | SCV004331388 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2023-04-22 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.006%). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DSC2 protein function. ClinVar contains an entry for this variant (Variation ID: 928379). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 49 of the DSC2 protein (p.Val49Ala). |