ClinVar Miner

Submissions for variant NM_000069.3(CACNA1S):c.1493G>A (p.Arg498His) (rs150590855)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000487733 SCV000574805 uncertain significance not provided 2016-10-01 criteria provided, single submitter clinical testing
Invitae RCV000697677 SCV000826302 uncertain significance Hypokalemic periodic paralysis 1; Malignant hyperthermia, susceptibility to, 5 2020-10-28 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 498 of the CACNA1S protein (p.Arg498His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs150590855, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with CACNA1S-related disease. ClinVar contains an entry for this variant (Variation ID: 424926). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Illumina Clinical Services Laboratory,Illumina RCV001096477 SCV001252693 uncertain significance Hypokalemic periodic paralysis 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Athena Diagnostics Inc RCV000487733 SCV001474977 likely benign not provided 2019-12-02 criteria provided, single submitter clinical testing
GeneDx RCV000487733 SCV001794674 uncertain significance not provided 2021-05-17 criteria provided, single submitter clinical testing Reported in an individual with exertional heat illness who harbored an additional variant in the CACNA1S gene and was not susceptible to malignant hyperthermia by in vitro contracture test (Fiszer et al., 2015); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function This variant is associated with the following publications: (PMID: 25658027)

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