ClinVar Miner

Submissions for variant NM_000540.3(RYR1):c.577T>A (p.Ser193Thr)

gnomAD frequency: 0.00001  dbSNP: rs886054379
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
Illumina Laboratory Services, Illumina RCV000347556 SCV000411838 uncertain significance Neuromuscular disease, congenital, with uniform type 1 fiber 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000391552 SCV000411839 uncertain significance Multiminicore myopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000312732 SCV000411840 uncertain significance Central core myopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000367447 SCV000411841 uncertain significance Malignant hyperthermia of anesthesia 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV001216385 SCV001388181 uncertain significance RYR1-related disorder 2021-08-28 criteria provided, single submitter clinical testing This sequence change replaces serine with threonine at codon 193 of the RYR1 protein (p.Ser193Thr). The serine residue is highly conserved and there is a small physicochemical difference between serine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 328993). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Fulgent Genetics, Fulgent Genetics RCV002495038 SCV002782495 uncertain significance Central core myopathy; Malignant hyperthermia, susceptibility to, 1; Congenital multicore myopathy with external ophthalmoplegia; Congenital myopathy with fiber type disproportion; King Denborough syndrome 2021-08-19 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV003995863 SCV004817860 uncertain significance Malignant hyperthermia, susceptibility to, 1 2023-07-10 criteria provided, single submitter clinical testing This missense variant replaces serine with threonine at codon 193 of the RYR1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RYR1-related disorders in the literature. This variant has been identified in 3/282310 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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.