ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.14693T>C (p.Ile4898Thr) (rs118192170)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 15
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PharmGKB RCV000786443 SCV000925265 drug response enflurane response - Toxicity/ADR reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PharmGKB RCV000786444 SCV000925266 drug response halothane response - Toxicity/ADR reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PharmGKB RCV000786445 SCV000925267 drug response isoflurane response - Toxicity/ADR reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PharmGKB RCV000786446 SCV000925268 drug response methoxyflurane response - Toxicity/ADR reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PharmGKB RCV000786447 SCV000925269 drug response sevoflurane response - Toxicity/ADR reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PharmGKB RCV000786448 SCV000925270 drug response succinylcholine response - Toxicity/ADR reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
PharmGKB RCV000786692 SCV000925514 drug response desflurane response - Toxicity/ADR reviewed by expert panel curation PharmGKB Level of Evidence 1A: Annotation for a variant-drug combination in a CPIC or medical society-endorsed PGx guideline, or implemented at a PGRN site or in another major health system.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000013843 SCV000611595 pathogenic Myopathy, Central Core 2017-10-12 criteria provided, single submitter research
Invitae RCV000535754 SCV000659857 pathogenic RYR1-Related Disorders 2018-09-04 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 4898 of the RYR1 protein (p.Ile4898Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is not present in population databases (rs118192170, ExAC no frequency). This variant has been reported to segregate with autosomal dominant central core disease (CCD) in several families (PMID: 10097181, 11709545, 11741831) and reported in several individuals affected with CCD (PMID: 25084811, 24561095). In addition, this variant has been shown to arise de novo in twins affected with core-rod myopathy (PMID: 20888934). This variant is also known as I4897T in the literature. ClinVar contains an entry for this variant (Variation ID: 12975). Experimental studies have shown that this missense change impacts the function of the RYR1 channel, and a knock-in mouse model recapitulated the central core disease phenotype (PMID: 10097181, 15175001, 12642598, 22203976, 21825032). This missense change is located in the C-terminal mutational hotspot of the RYR1 protein where a significant number of previously reported RYR1 missense mutations are found (PMID: 16084090). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics,PreventionGenetics RCV000119552 SCV000852452 pathogenic not provided 2016-08-15 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763430 SCV000894195 pathogenic Myopathy, Central Core; Malignant hyperthermia, susceptibility to, 1; Minicore myopathy; Congenital myopathy with fiber type disproportion 2018-10-31 criteria provided, single submitter clinical testing
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV000013844 SCV000928375 likely pathogenic Malignant hyperthermia, susceptibility to, 1 2018-09-27 criteria provided, single submitter clinical testing PM1, PM2, PP3, PP4, PP5
OMIM RCV000013843 SCV000034090 pathogenic Myopathy, Central Core 2001-12-01 no assertion criteria provided literature only
OMIM RCV000013844 SCV000034091 risk factor Malignant hyperthermia, susceptibility to, 1 2001-12-01 no assertion criteria provided literature only
Leiden Muscular Dystrophy (RYR1) RCV000119552 SCV000154459 not provided not provided no assertion provided not provided

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.