ClinVar Miner

Submissions for variant NM_000069.3(CACNA1S):c.4796G>A (p.Arg1599Gln)

gnomAD frequency: 0.00002  dbSNP: rs946904077
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001955215 SCV002211952 uncertain significance Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 2023-10-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1599 of the CACNA1S protein (p.Arg1599Gln). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CACNA1S-related conditions. ClinVar contains an entry for this variant (Variation ID: 1435020). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Fulgent Genetics, Fulgent Genetics RCV002484662 SCV002791299 uncertain significance Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5; Thyrotoxic periodic paralysis, susceptibility to, 1 2021-12-07 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003452208 SCV004181063 uncertain significance Malignant hyperthermia, susceptibility to, 5 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003456265 SCV004181065 uncertain significance Thyrotoxic periodic paralysis, susceptibility to, 1 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003458797 SCV004181066 uncertain significance Congenital myopathy 18 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003456264 SCV004181067 uncertain significance Hypokalemic periodic paralysis, type 1 2023-04-11 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003452208 SCV004819851 uncertain significance Malignant hyperthermia, susceptibility to, 5 2024-08-06 criteria provided, single submitter clinical testing This missense variant replaces arginine with glutamine at codon 1599 of the CACNA1S protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 7/282554 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.

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