ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.877G>A (p.Gly293Arg)

dbSNP: rs121908215
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001388786 SCV001589919 pathogenic Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2024-06-05 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 293 of the CACNA1A protein (p.Gly293Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of episodic ataxia type 2 (PMID: 9345107; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 8496). 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%. Experimental studies have shown that this missense change affects CACNA1A function (PMID: 11742003, 15985579, 18434528). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV004700207 SCV005201905 likely pathogenic not provided 2024-01-30 criteria provided, single submitter clinical testing Published functional studies demonstrate altered channel function (PMID: 15985579); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 11742003, 11179022, 16325861, 18602318, 32899500, 12707077, 32116539, 9345107, 15985579)
OMIM RCV000009018 SCV000029233 pathogenic Spinocerebellar ataxia type 6 2005-06-28 no assertion criteria provided literature only
OMIM RCV000009019 SCV000029234 pathogenic Episodic ataxia type 2 2005-06-28 no assertion criteria provided literature only
UniProtKB/Swiss-Prot RCV000009018 SCV000090877 not provided Spinocerebellar ataxia type 6 no assertion provided not provided

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