ClinVar Miner

Submissions for variant NM_000069.3(CACNA1S):c.2366G>A (p.Arg789His)

gnomAD frequency: 0.00001  dbSNP: rs1157720606
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV001254711 SCV001430780 uncertain significance Muscular atrophy; skeletal contractures 2020-05-29 criteria provided, single submitter research The homozygous p.Arg789His variant in CACNA1S was identified by our study in 2 siblings with skeletal muscle atrophy and contractures. These Turkish siblings, along with an affected relative who was also homozygous for the p.Arg789His variant, were reported in the literature (PMID: 31227654). This variant has been identified in 0.0013% (1/75812) of European (Non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PM3_supporting, PP3 (Richards 2015).
Revvity Omics, Revvity RCV003456486 SCV003828856 uncertain significance not provided 2022-01-20 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003449815 SCV004177896 uncertain significance Malignant hyperthermia, susceptibility to, 5 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003449816 SCV004177897 uncertain significance Thyrotoxic periodic paralysis, susceptibility to, 1 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003152617 SCV004177898 uncertain significance Congenital myopathy 18 2023-04-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV003145495 SCV004177899 uncertain significance Hypokalemic periodic paralysis, type 1 2023-04-11 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV003456486 SCV004183997 likely pathogenic not provided 2023-11-01 criteria provided, single submitter clinical testing CACNA1S: PM2, PM3, PM5, PP3
All of Us Research Program, National Institutes of Health RCV003449815 SCV004825045 uncertain significance Malignant hyperthermia, susceptibility to, 5 2023-08-15 criteria provided, single submitter clinical testing
OMIM RCV003152617 SCV003841111 pathogenic Congenital myopathy 18 2024-07-16 no assertion criteria provided literature only

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