ClinVar Miner

Submissions for variant NM_000540.2(RYR1):c.1654C>T (p.Arg552Trp) (rs193922770)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000536735 SCV000659871 pathogenic RYR1-Related Disorders 2017-03-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 552 of the RYR1 protein (p.Arg552Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). ClinVar contains an entry for this variant (Variation ID: 133106). This variant has been reported to segregate with malignant hyperthermia susceptibility (MHS) in a single family (PMID: 9138151). It has also been reported in an unrelated MHS patient (PMID: 16244001) and an affected individual at Invitae (Invitae database). Experimental studies have shown that this missense change increases the sensitivity of RYR1 channel-mediated calcium release in response to caffeine or halothane stimulation (PMID: 9334205). In addition, this missense change is located in an N-terminal region of the RYR1 protein where many other previously reported MHS-associated mutations have been found (PMID: 16084090). For these reasons, this variant has been classified as Pathogenic.
Leiden Muscular Dystrophy (RYR1) RCV000119581 SCV000154488 not provided not provided no assertion provided not provided
PharmGKB RCV000786667 SCV000925489 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 RCV000786668 SCV000925490 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 RCV000786710 SCV000925532 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 RCV000786711 SCV000925533 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 RCV000786712 SCV000925534 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 RCV000786713 SCV000925535 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 RCV000786714 SCV000925536 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.

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