Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003805243 | SCV004606941 | pathogenic | Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 | 2023-10-27 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1392 of the CACNA1A protein (p.Ala1392Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of CACNA1A-related conditions (Invitae). In at least one individual the variant was observed to be de novo. 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 with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |