Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001942154 | SCV002236310 | pathogenic | Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 | 2023-05-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. 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: 1454996). This missense change has been observed in individual(s) with CACNA1A-related conditions (PMID: 25596066). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 272 of the CACNA1A protein (p.Cys272Tyr). |
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV002291304 | SCV002583725 | likely pathogenic | CACNA1A-related disorder | 2022-09-28 | criteria provided, single submitter | clinical testing | PM6 PM2 PS4_moderate PP2 PP3 |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004782836 | SCV005394921 | likely pathogenic | Hereditary episodic ataxia | 2024-09-11 | criteria provided, single submitter | clinical testing | Variant summary: CACNA1A c.815G>A (p.Cys272Tyr) results in a non-conservative amino acid change located in the Ion transport domain (IPR005821) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 178730 control chromosomes (gnomAD). c.815G>A has been reported in the literature in individuals affected with Episodic Ataxia or infantile-onset epilepsy (e.g. Blumkin_2015, Kuperberg_2016, Daniels_2024), in one case as a de novo occurrence. These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 25596066, 27572814, 37771170). ClinVar contains an entry for this variant (Variation ID: 1454996). Based on the evidence outlined above, the variant was classified as likely pathogenic. |