ClinVar Miner

Submissions for variant NM_000069.3(CACNA1S):c.3715C>G (p.Arg1239Gly)

dbSNP: rs28930069
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000518061 SCV000612604 pathogenic not provided 2014-06-02 criteria provided, single submitter clinical testing
Invitae RCV000693727 SCV000821608 pathogenic Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 2021-10-04 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg1239 amino acid residue in CACNA1S. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7847370, 17418573, 19225109). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 17624). This missense change has been observed in individual(s) with hypokalemic periodic paralysis (PMID: 8004673, 15716625, 18162704, 18229654). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glycine at codon 1239 of the CACNA1S protein (p.Arg1239Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine.
GeneDx RCV000518061 SCV001780892 pathogenic not provided 2021-07-20 criteria provided, single submitter clinical testing Recurrent variant associated with hypokalemic periodic paralysis (Matthews et al., 2009); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed in large population cohorts (Lek et al., 2016) This variant is associated with the following publications: (PMID: 15221887, 26252573, 15711422, 19779499, 18229654, 15716625, 19118277, 20301512, 11353725, 8004673, 21891927)
Genome-Nilou Lab RCV003450646 SCV004177655 pathogenic Malignant hyperthermia, susceptibility to, 5 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000019191 SCV004177656 pathogenic Hypokalemic periodic paralysis, type 1 2023-04-11 criteria provided, single submitter clinical testing
OMIM RCV000019191 SCV000039479 pathogenic Hypokalemic periodic paralysis, type 1 1994-06-17 no assertion criteria provided literature only
GeneReviews RCV000019191 SCV000040411 not provided Hypokalemic periodic paralysis, type 1 no assertion provided literature only

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