ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.633T>C (p.Ser211=)

gnomAD frequency: 0.00005  dbSNP: rs202216404
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000727523 SCV000709448 uncertain significance not provided 2017-06-16 criteria provided, single submitter clinical testing
GeneDx RCV000727523 SCV000728238 likely benign not provided 2019-07-12 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 31719132)
Ambry Genetics RCV002311954 SCV000847142 likely benign Inborn genetic diseases 2016-07-26 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp RCV001082686 SCV001046027 likely benign Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2023-12-18 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004782468 SCV005395002 likely benign not specified 2024-09-10 criteria provided, single submitter clinical testing Variant summary: CACNA1A c.633T>C (p.Ser211Ser) alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 6e-05 in 248420 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in CACNA1A causing Epileptic Encephalopathy, Early Infantile, 42, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.633T>C in individuals affected with Epileptic Encephalopathy, Early Infantile, 42 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 502635). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences RCV003985385 SCV004721728 likely benign CACNA1A-related disorder 2020-08-20 no assertion criteria provided clinical testing This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

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