Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000458553 | SCV000552081 | uncertain significance | Brugada syndrome | 2021-01-05 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with methionine at codon 714 of the CACNA2D1 protein (p.Ile714Met). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and methionine. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with CACNA2D1-related conditions. ClinVar contains an entry for this variant (Variation ID: 411090). This variant is present in population databases (rs745501384, ExAC 0.003%). |
| Ambry Genetics | RCV003168844 | SCV003856735 | uncertain significance | Cardiovascular phenotype | 2022-11-27 | criteria provided, single submitter | clinical testing | The p.I714M variant (also known as c.2142C>G) is located in coding exon 27 of the CACNA2D1 gene. The isoleucine at codon 714 is replaced by methionine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 27. 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. |