Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001186582 | SCV001353045 | uncertain significance | Cardiomyopathy | 2023-10-19 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with serine at codon 970 of the DSG2 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 not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/241458 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. |
Labcorp Genetics |
RCV001862937 | SCV002295603 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2022-10-13 | 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 not expected to disrupt DSG2 protein function. ClinVar contains an entry for this variant (Variation ID: 924924). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. This variant is present in population databases (rs758058872, gnomAD 0.01%). This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 970 of the DSG2 protein (p.Pro970Ser). |
All of Us Research Program, |
RCV004008613 | SCV004821850 | uncertain significance | Arrhythmogenic right ventricular cardiomyopathy | 2023-11-02 | criteria provided, single submitter | clinical testing | Variant of Uncertain Significance due to insufficient evidence: This missense variant replaces proline with serine at codon 970 of the DSG2 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 2/241458 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. |