Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002457642 | SCV002738043 | uncertain significance | Cardiovascular phenotype | 2024-04-30 | criteria provided, single submitter | clinical testing | The p.S778A variant (also known as c.2332T>G), located in coding exon 29 of the CACNA2D1 gene, results from a T to G substitution at nucleotide position 2332. The serine at codon 778 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |
| Labcorp Genetics |
RCV005098082 | SCV005770079 | uncertain significance | Brugada syndrome | 2024-08-07 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 778 of the CACNA2D1 protein (p.Ser778Ala). This variant is present in population databases (no rsID available, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CACNA2D1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1789745). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |