Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001234011 | SCV001406636 | uncertain significance | Long QT syndrome | 2022-04-04 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 794 of the CACNA1C protein (p.Pro794Leu). This variant is present in population databases (rs771393283, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CACNA1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 960479). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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. |
| Ambry Genetics | RCV002451560 | SCV002737792 | uncertain significance | Cardiovascular phenotype | 2023-03-01 | criteria provided, single submitter | clinical testing | The p.P794L variant (also known as c.2381C>T), located in coding exon 17 of the CACNA1C gene, results from a C to T substitution at nucleotide position 2381. The proline at codon 794 is replaced by leucine, an amino acid with similar properties. This amino acid position is well 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. |