ClinVar Miner

Submissions for variant NM_000069.3(CACNA1S):c.4340G>A (p.Arg1447Gln)

gnomAD frequency: 0.00014  dbSNP: rs377474103
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000651224 SCV000773075 uncertain significance Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5 2023-11-28 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1447 of the CACNA1S protein (p.Arg1447Gln). This variant is present in population databases (rs377474103, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of metabolic myopathy (PMID: 30325262). ClinVar contains an entry for this variant (Variation ID: 541040). 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 disruptive. 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 RCV001574964 SCV001801868 uncertain significance not provided 2023-03-07 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign in association with a CACNA1S-related disorder to our knowledge; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; This variant is associated with the following publications: (PMID: 31851124, 36833203, 30325262)
Fulgent Genetics, Fulgent Genetics RCV002507121 SCV002814961 uncertain significance Hypokalemic periodic paralysis, type 1; Malignant hyperthermia, susceptibility to, 5; Thyrotoxic periodic paralysis, susceptibility to, 1 2022-02-15 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003451555 SCV004181147 uncertain significance Malignant hyperthermia, susceptibility to, 5 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003451556 SCV004181148 uncertain significance Thyrotoxic periodic paralysis, susceptibility to, 1 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003458485 SCV004181149 uncertain significance Congenital myopathy 18 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003456115 SCV004181150 uncertain significance Hypokalemic periodic paralysis, type 1 2023-04-11 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.