Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000480974 | SCV000570511 | uncertain significance | not provided | 2016-05-25 | criteria provided, single submitter | clinical testing | The K995Q variant in the CACNA2D1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The K995Q variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The K995Q variant is a semi-conservative amino acid substitution, which occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. |
| Labcorp Genetics |
RCV001865458 | SCV002173620 | uncertain significance | Brugada syndrome | 2021-01-25 | 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. This sequence change replaces lysine with glutamine at codon 995 of the CACNA2D1 protein (p.Lys995Gln). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CACNA2D1-related conditions. ClinVar contains an entry for this variant (Variation ID: 421337). 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: "Probably Damaging"; Align-GVGD: "Class C0"). |