ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.5015G>C (p.Arg1672Pro)

dbSNP: rs1057519429
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Wendy Chung Laboratory, Columbia University Medical Center RCV002227158 SCV002506552 likely pathogenic Episodic ataxia type 2; Spinocerebellar ataxia type 6; Migraine, familial hemiplegic, 1; Developmental and epileptic encephalopathy, 52 2022-03-20 criteria provided, single submitter clinical testing
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000416438 SCV000494150 pathogenic Cerebellar ataxia no assertion criteria provided research This variant was identified, de novo, in an individual with non-fluctuating ataxia.
Undiagnosed Diseases Network, NIH RCV000556499 SCV000622144 likely pathogenic Cerebellar ataxia; Intellectual disability; Cerebellar atrophy 2015-12-19 no assertion criteria provided clinical testing Likely pathogenicity based on finding it once in our study de novo in an 8-year-old female with delayed motor milestones, delayed speech, progressive cerebellar atrophy, hypotonia, and problems with coordination. Our patient has been reported in PMCID:PMC5557584 (patient 1).
PreventionGenetics, part of Exact Sciences RCV004725207 SCV005339107 likely pathogenic CACNA1A-related disorder 2024-08-10 no assertion criteria provided clinical testing The CACNA1A c.5015G>C variant is predicted to result in the amino acid substitution p.Arg1672Pro. This variant has been confirmed to be de novo in two unrelated individuals with CACNA1A-related disorders (Eldomery et al. 2017. PubMed ID: 28327206; Luo et al. 2017. PubMed ID: 28742085). In vivo modeling of this variant showed alternation in channel activation consistent with a gain-of-function effect (Luo et al. 2017. PubMed ID: 28742085; Tyagi et al. 2019. PubMed ID: 31015257). This variant has not been reported in a large population database, indicating this variant is rare and it is classified as likely pathogenic/pathogenic in ClinVar. Given the evidence, we interpret this variant as likely pathogenic.

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