Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001177857 | SCV001342139 | likely benign | Cardiomyopathy | 2020-04-14 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001875863 | SCV002206609 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2022-08-03 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 813 of the DSC2 protein (p.His813Pro). This variant is present in population databases (rs766881629, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with DSC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 919602). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Ambry Genetics | RCV002451363 | SCV002736707 | uncertain significance | Cardiovascular phenotype | 2020-03-26 | criteria provided, single submitter | clinical testing | The p.H813P variant (also known as c.2438A>C), located in coding exon 15 of the DSC2 gene, results from an A to C substitution at nucleotide position 2438. The histidine at codon 813 is replaced by proline, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
All of Us Research Program, |
RCV004006419 | SCV004816047 | likely benign | Familial isolated arrhythmogenic right ventricular dysplasia | 2023-12-13 | criteria provided, single submitter | clinical testing |