Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003022030 | SCV003316744 | uncertain significance | Arrhythmogenic right ventricular dysplasia 11 | 2022-02-25 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; 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. This variant has not been reported in the literature in individuals affected with DSC2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 358 of the DSC2 protein (p.Thr358Pro). |
| Ambry Genetics | RCV003170889 | SCV003853624 | uncertain significance | Cardiovascular phenotype | 2023-01-29 | criteria provided, single submitter | clinical testing | The p.T358P variant (also known as c.1072A>C), located in coding exon 8 of the DSC2 gene, results from an A to C substitution at nucleotide position 1072. The threonine at codon 358 is replaced by proline, 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. |