ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.6397C>T (p.Arg2133Ter)

dbSNP: rs1555730878
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522787 SCV000622069 pathogenic not provided 2023-10-10 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002271522 SCV002555787 likely pathogenic Developmental and epileptic encephalopathy, 42 2022-06-09 criteria provided, single submitter clinical testing Variant summary: CACNA1A c.6400C>T (p.Arg2134X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been cited as pathogenic/likely pathogenic in ClinVar (e.g. p.Glu2165X, p.Arg2124LeufsX59, p.Asp2138X, p.Arg2134TrpfsX47) (Variation IDs: 451719, 520922, 995297, 1072305). Furthermore, deletions involving the exon where this variant is located (i.e. exon 45) and/or downstream exons (i.e. exons 46 and 47) have been reported in the literature in multiple individuals affected with hemiplegic migraine, episodic ataxia, and migraine with or without Aura (i.e. ex45-47del, ex46-47del and ex47del) (PMID: 30167989). The variant was absent in 152174 control chromosomes (gnomAD v3.1, Genomes dataset). To our knowledge, no occurrence of c.6400C>T in individuals affected with Epileptic Encephalopathy, Early Infantile, 42 and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.