Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002445723 | SCV002612565 | uncertain significance | Cardiovascular phenotype | 2024-07-19 | criteria provided, single submitter | clinical testing | The c.3274T>C variant (also known as p.*1092Rext*25), located in coding exon 39 of the CACNA2D1 gene, results from a T to C substitution at nucleotide position 3274. This alteration disrupts the stop codon of the CACNA2D1 gene and is predicted to preserve the native sequence while resulting in the elongation of the protein by 25 amino acids. The exact functional effect of the additional amino acids is unknown. In addition, loss of function of CACNA2D1 has not been clearly established as a mechanism of disease. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |
| Labcorp Genetics |
RCV003099353 | SCV003460673 | uncertain significance | Brugada syndrome | 2025-01-07 | criteria provided, single submitter | clinical testing | This sequence change disrupts the translational stop signal of the CACNA2D1 mRNA. It is expected to extend the length of the CACNA2D1 protein by 25 additional amino acid residues. This variant is present in population databases (rs759988243, gnomAD 0.003%). 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: 1729659). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |