Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001327507 | SCV001518586 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2020-09-11 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs150124218, ExAC 0.01%). This sequence change replaces histidine with arginine at codon 803 of the DSC2 protein (p.His803Arg). The histidine residue is moderately conserved and there is a small physicochemical difference between histidine and arginine. This variant has not been reported in the literature in individuals with DSC2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 | RCV002447380 | SCV002732701 | uncertain significance | Cardiovascular phenotype | 2022-01-10 | criteria provided, single submitter | clinical testing | The p.H803R variant (also known as c.2408A>G), located in coding exon 15 of the DSC2 gene, results from an A to G substitution at nucleotide position 2408. The histidine at codon 803 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. 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. |