Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001574150 | SCV001800912 | likely benign | not provided | 2020-05-04 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
New York Genome Center | RCV001839050 | SCV002099102 | uncertain significance | Developmental and epileptic encephalopathy, 42 | 2021-03-05 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002573226 | SCV003001899 | uncertain significance | Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 | 2021-12-09 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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 not expected to disrupt CACNA1A protein function. ClinVar contains an entry for this variant (Variation ID: 1206480). This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 939 of the CACNA1A protein (p.Gly939Asp). |