ClinVar Miner

Submissions for variant NM_000069.3(CACNA1S):c.1345A>G (p.Ile449Val)

gnomAD frequency: 0.00006  dbSNP: rs369139165
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001066686 SCV001231702 likely benign Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 2023-04-07 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001531029 SCV001745966 uncertain significance not provided 2021-05-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002482104 SCV002776916 uncertain significance Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5; Thyrotoxic periodic paralysis, susceptibility to, 1 2022-03-24 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV004000161 SCV004822992 uncertain significance Malignant hyperthermia, susceptibility to, 5 2023-08-15 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 449 of the CACNA1S protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 2/251460 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.
Ambry Genetics RCV004030622 SCV004915020 uncertain significance Inborn genetic diseases 2023-12-18 criteria provided, single submitter clinical testing The c.1345A>G (p.I449V) alteration is located in exon 10 (coding exon 10) of the CACNA1S gene. This alteration results from a A to G substitution at nucleotide position 1345, causing the isoleucine (I) at amino acid position 449 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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