Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002029819 | SCV002110479 | likely pathogenic | not provided | 2020-12-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine with valine at codon 690 of the CACNA1E protein (p.Gly690Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CACNA1E-related conditions. 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 CACNA1E protein function. This variant disrupts the p.Gly690 amino acid residue in CACNA1E. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 30343943). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. |