ClinVar Miner

Submissions for variant NM_000069.3(CACNA1S):c.2582G>C (p.Gly861Ala)

gnomAD frequency: 0.00011  dbSNP: rs369192794
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000425186 SCV000526534 uncertain significance not provided 2018-07-05 criteria provided, single submitter clinical testing The G861A variant in the CACNA1S gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The G861A variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G861A variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret G861A as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001861555 SCV002263569 benign Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 2023-10-04 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004000425 SCV004832894 uncertain significance Malignant hyperthermia, susceptibility to, 5 2023-12-01 criteria provided, single submitter clinical testing This missense variant replaces glycine with alanine at codon 861 of the CACNA1S protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with CACNA1S-related disorders in the literature. This variant has been identified in 10/282758 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Breakthrough Genomics, Breakthrough Genomics RCV000425186 SCV005187151 uncertain significance not provided criteria provided, single submitter not provided

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