ClinVar Miner

Submissions for variant NM_000069.3(CACNA1S):c.982C>A (p.Leu328Met)

dbSNP: rs1558078309
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000684971 SCV000812437 uncertain significance Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 2018-06-22 criteria provided, single submitter clinical testing This sequence change replaces leucine with methionine at codon 328 of the CACNA1S protein (p.Leu328Met). The leucine residue is highly conserved and there is a small physicochemical difference between leucine and methionine. 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. 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"). This variant has not been reported in the literature in individuals with CACNA1S-related disease. This variant is not present in population databases (ExAC no frequency).
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine RCV003338729 SCV004047467 uncertain significance Thyrotoxic periodic paralysis, susceptibility to, 1 criteria provided, single submitter clinical testing The missense variant in c.982C>A (p.Leu328Met) in CACNA1S gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Leu328Met variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Uncertain Significance. The amino acid Leu at position 328 is changed to a Met changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Leu328Met in CACNA1S is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as uncertain significance. This variant was identified in the proband in heterozygous state. This variant is also identified in asymptomatic mother, it is not likely to cause the disease.
Genome-Nilou Lab RCV003456126 SCV004179198 uncertain significance Malignant hyperthermia, susceptibility to, 5 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003338729 SCV004179199 uncertain significance Thyrotoxic periodic paralysis, susceptibility to, 1 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003458499 SCV004179200 uncertain significance Congenital myopathy 18 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003453403 SCV004179201 uncertain significance Hypokalemic periodic paralysis, type 1 2023-04-11 criteria provided, single submitter clinical testing

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