Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000686079 | SCV000813582 | pathogenic | Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 | 2023-12-18 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 297 of the CACNA1A protein (p.Gly297Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with episodic ataxia (PMID: 26814174, 28431595, 30891074). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 566307). 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. |
| Athena Diagnostics | RCV000710984 | SCV000841300 | uncertain significance | not provided | 2020-02-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000710984 | SCV001779624 | pathogenic | not provided | 2022-04-27 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26814174, 29482223, 28431595, 30891074, 32116539, 32899500, 34507393, 34263451) |