ClinVar Miner

Submissions for variant NM_000069.3(CACNA1S):c.732del (p.Cys245fs)

dbSNP: rs1558079311
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000801288 SCV000941059 pathogenic Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 2023-06-03 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 646905). This variant has not been reported in the literature in individuals affected with CACNA1S-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys245Alafs*89) in the CACNA1S gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CACNA1S are known to be pathogenic (PMID: 26247046, 28012042).
All of Us Research Program, National Institutes of Health RCV004001640 SCV004834587 uncertain significance Malignant hyperthermia, susceptibility to, 5 2024-09-23 criteria provided, single submitter clinical testing This variant deletes 1 nucleotide in exon 6 of the CACNA1S gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with CACNA1S-related disorders in the literature. This variant has been identified in 1/250584 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of CACNA1S function due to truncation variants is not an established disease mechanism for autosomal dominant malignant hyperthermia, although it is associated with other phenotype(s) (ClinVar variation ID: 646905). Due to insufficient evidence, this variant is classified as a Variant of Uncertain Significance for autosomal dominant malignant hyperthermia.

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