Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000699444 | SCV000828156 | uncertain significance | Long QT syndrome | 2023-08-28 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with CACNA1C-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CACNA1C protein function. ClinVar contains an entry for this variant (Variation ID: 576846). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 2115 of the CACNA1C protein (p.Gly2115Asp). |
| Ambry Genetics | RCV002360789 | SCV002660684 | uncertain significance | Cardiovascular phenotype | 2022-10-04 | criteria provided, single submitter | clinical testing | The p.G2115D variant (also known as c.6344G>A), located in coding exon 47 of the CACNA1C gene, results from a G to A substitution at nucleotide position 6344. The glycine at codon 2115 is replaced by aspartic acid, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. 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. |