ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.487C>T (p.Arg163Cys) (rs118192161)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 13
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000119625 SCV000567432 pathogenic not provided 2015-08-28 criteria provided, single submitter clinical testing The R163C substitution in the RYR1 gene has been published previously as a pathogenic variantassociated with malignant hyperthermia (Broman et al., 2011; Carpenter et al., 2009; Monnier et al., 2002; Quane et al., 1993). Based on the ACMG recommendations, R163C is interpreted as a pathogenic variant.
Invitae RCV000806352 SCV000946344 pathogenic RYR1-Related Disorders 2018-11-09 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 163 of the RYR1 protein (p.Arg163Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with malignant hyperthermia (MH) and central core disease (CCD) in several families and has been reported in numerous individuals affected with either MH or CCD (PMID: 8220423, 8592342, 19648156). ClinVar contains an entry for this variant (Variation ID: 12967). Experimental studies have shown that this missense change alters protein function in vitro and in vivo (PMID: 21156754, 9334205, 11524458). This missense change is located in a region of the RYR1 protein where a significant number of previously reported RYR1 missense mutations are found (PMID: 16917943, 12565913, 23919265). These observations suggest that a previously unreported missense substitution within this region may affect protein function. For these reasons, this variant has been classified as Pathogenic.
Leiden Muscular Dystrophy (RYR1) RCV000119625 SCV000154532 not provided not provided no assertion provided not provided
OMIM RCV000013833 SCV000034080 risk factor Malignant hyperthermia, susceptibility to, 1 2001-07-11 no assertion criteria provided literature only
OMIM RCV000013834 SCV000034081 pathogenic Myopathy, Central Core 2001-07-11 no assertion criteria provided literature only
PharmGKB RCV000786435 SCV000925257 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 RCV000786436 SCV000925258 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 RCV000786632 SCV000925454 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.
PharmGKB RCV000786633 SCV000925455 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 RCV000786634 SCV000925456 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 RCV000786635 SCV000925457 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 RCV000786636 SCV000925458 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.
PreventionGenetics RCV000119625 SCV000852652 pathogenic not provided 2016-11-14 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.