ClinVar Miner

Submissions for variant NM_000069.3(CACNA1S):c.1481C>T (p.Ser494Phe)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
All of Us Research Program, National Institutes of Health RCV004805670 SCV005426068 uncertain significance Malignant hyperthermia, susceptibility to, 5 2024-08-06 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005221016 SCV005868406 uncertain significance Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 2024-03-26 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 494 of the CACNA1S protein (p.Ser494Phe). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with CACNA1S-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CACNA1S protein function with a negative predictive value of 80%. 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.
PreventionGenetics, part of Exact Sciences RCV004732457 SCV005339097 uncertain significance CACNA1S-related disorder 2024-07-20 no assertion criteria provided clinical testing The CACNA1S c.1481C>T variant is predicted to result in the amino acid substitution p.Ser494Phe. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0054% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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