ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.1427G>A (p.Arg476His)

gnomAD frequency: 0.00001  dbSNP: rs755107633
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001048359 SCV001212360 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2024-12-28 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 477 of the CACNA1A protein (p.Arg477His). This variant is present in population databases (rs755107633, gnomAD 0.01%). This missense change has been observed in individual(s) with idiopathic epilepsy (PMID: 21703448). ClinVar contains an entry for this variant (Variation ID: 845317). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt CACNA1A protein function with a positive predictive value of 95%. 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.
GeneDx RCV001570122 SCV001794343 likely benign not provided 2019-05-17 criteria provided, single submitter clinical testing Reported as a novel variant in a cohort of epilepsy patients; additional information was not provided (Klassen et al., 2011); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 28488083, 21703448)
Athena Diagnostics RCV001570122 SCV002770831 uncertain significance not provided 2022-03-31 criteria provided, single submitter clinical testing

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