ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.593G>A (p.Arg198Gln)

dbSNP: rs797045424
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000194067 SCV000246838 uncertain significance not specified 2015-01-09 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000764184 SCV000895186 uncertain significance Episodic ataxia type 2; Spinocerebellar ataxia type 6; Migraine, familial hemiplegic, 1; Developmental and epileptic encephalopathy, 42 2018-10-31 criteria provided, single submitter clinical testing
Athena Diagnostics RCV001289293 SCV001477021 uncertain significance not provided 2020-08-28 criteria provided, single submitter clinical testing
Invitae RCV003765213 SCV004574057 likely pathogenic Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2023-05-02 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 198 of the CACNA1A protein (p.Arg198Gln). ClinVar contains an entry for this variant (Variation ID: 210556). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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. This missense change has been observed in individuals with clinical features of autosomal dominant CACNA1A-related conditions (PMID: 30063100, 30692599, 33163565).
GeneDx RCV001289293 SCV005078041 uncertain significance not provided 2023-12-19 criteria provided, single submitter clinical testing 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: 33163565, 29915382, 30063100, 32116539, 30692599, 34068417)

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