Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001217912 | SCV001389772 | likely pathogenic | Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 | 2022-07-25 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Val1456 amino acid residue in CACNA1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10408532, 10734061). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 expected to disrupt CACNA1A protein function. ClinVar contains an entry for this variant (Variation ID: 946947). This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1456 of the CACNA1A protein (p.Val1456Met). |
| Génétique des Maladies du Développement, |
RCV004587073 | SCV005077698 | likely pathogenic | Seizure | 2024-06-20 | criteria provided, single submitter | clinical testing |