Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001182583 | SCV001348094 | uncertain significance | Cardiomyopathy | 2023-12-04 | criteria provided, single submitter | clinical testing | This missense variant replaces histidine with arginine at codon 43 of the DSG2 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 DSG2-related disorders in the literature. This variant has been identified in 2/249494 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 |
RCV001773429 | SCV001992703 | uncertain significance | not provided | 2019-06-11 | criteria provided, single submitter | clinical testing | 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; Has not been previously published as pathogenic or benign to our knowledge |
Fulgent Genetics, |
RCV002505775 | SCV002813441 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10; Dilated cardiomyopathy 1BB | 2021-11-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003631184 | SCV004526595 | uncertain significance | Arrhythmogenic right ventricular dysplasia 10 | 2023-12-13 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 43 of the DSG2 protein (p.His43Arg). This variant is present in population databases (rs370922106, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with DSG2-related conditions. ClinVar contains an entry for this variant (Variation ID: 922473). 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 with a negative predictive value of 95%. 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. |