ClinVar Miner

Submissions for variant NM_000069.3(CACNA1S):c.4972_4973delinsTA (p.Arg1658Tyr)

dbSNP: rs1553248123
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000651226 SCV000773077 uncertain significance Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 2024-01-10 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 1658 of the CACNA1S protein (p.Arg1658Tyr). This variant is present in population databases (no rsID available, gnomAD 0.03%). 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: 541041). 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.
GeneDx RCV001557016 SCV001778703 uncertain significance not provided 2021-12-07 criteria provided, single submitter clinical testing In silico analysis supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics RCV002499117 SCV002809971 uncertain significance Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5; Thyrotoxic periodic paralysis, susceptibility to, 1 2022-01-18 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003411537 SCV004113363 uncertain significance CACNA1S-related condition 2022-10-11 criteria provided, single submitter clinical testing The CACNA1S c.4972_4973delinsTA variant is predicted to result in an in-frame deletion and insertion. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. However, c.4972C>T (p.Arg1658Cys) and c.4973G>A (p.Arg1658His) which occur at this same codon have been reported at minor allele frequencies that are inconsistent with autosomal dominant inheritance (https://gnomad.broadinstitute.org/variant/chr1-201012485-G-A; https://gnomad.broadinstitute.org/variant/chr1-201012484-C-T). This could indicate that this amino acid residue is tolerant to variation. Although we suspect this variant could be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Genome-Nilou Lab RCV003451558 SCV004181040 uncertain significance Malignant hyperthermia, susceptibility to, 5 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003451559 SCV004181042 uncertain significance Thyrotoxic periodic paralysis, susceptibility to, 1 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003458486 SCV004181043 uncertain significance Congenital myopathy 18 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003451557 SCV004181044 uncertain significance Hypokalemic periodic paralysis, type 1 2023-04-11 criteria provided, single submitter clinical testing

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