Variant: NM_000540.2(RYR1):c.51_53del (p.Asp17del)

CA024489

133146 (ClinVar)

Gene: RYR1

Condition: malignant hyperthermia of anesthesia

Inheritance Mode: Autosomal dominant inheritance

UUID: 351325ce-27b8-4d6a-82d2-536e3213e439

Approved on: 2023-04-06

Published on: 2023-04-06

HGVS expressions

NM_000540.2:c.51_53del
NM_000540.2(RYR1):c.51_53del (p.Asp17del)
NC_000019.10:g.38440750_38440752del
CM000681.2:g.38440750_38440752del
NC_000019.9:g.38931390_38931392del
CM000681.1:g.38931390_38931392del
NC_000019.8:g.43623230_43623232del
NG_008866.1:g.12051_12053del
ENST00000599547.6:n.51_53del
ENST00000359596.8:c.51_53del
ENST00000355481.8:c.51_53del
ENST00000359596.7:n.51_53del
ENST00000360985.7:c.51_53del
NM_001042723.1:c.51_53del
NM_000540.3:c.51_53del
NM_001042723.2:c.51_53del
NM_000540.3(RYR1):c.51_53del (p.Asp17del)

Uncertain Significance

• Met criteria codes: PM1

• Not Met criteria codes: PS4

Expert Panel

Malignant Hyperthermia Susceptibility VCEP

Criteria Specification Information

Evidence submitted by expert panel

Malignant Hyperthermia Susceptibility VCEP

This pathogenicity assessment is relevant only for malignant hyperthermia susceptibility (MHS) inherited in an autosomal dominant pattern. Variants in RYR1 can also cause other myopathies inherited in an autosomal dominant pattern or in an autosomal recessive pattern. Some of these disorders may predispose individuals to malignant hyperthermia. RYR1 variants may also contribute to a malignant hyperthermia reaction in combination with other genetic and non-genetic factors and the clinician needs to consider such factors in making management decisions. This sequence variant predicts a deletion of aspartic acid at codon 17 of the RYR1 protein, p.(Asp17del). This variant was not present in a large population database (gnomAD) at the time this variant was interpreted. This variant has been reported in an individual with a personal or family history of an MH episode without a positive in vitro contracture test (IVCT) or caffeine halothane contracture test (CHCT) result, PS4 was not met (PMID:16732084). No functional studies were identified for this variant. This variant resides in a region of RYR1 considered to be a hotspot for pathogenic variants that contribute to MHS, PM1 (PMID: 21118704). This variant has been classified as a Variant of Unknown Significance. Criteria implemented: PM1.

Met criteria codes

• PM1: This variant resides in a region of RYR1 considered to be a hotspot for pathogenic variants that contribute to MHS, PM1 (PMID: 21118704).

Not Met criteria codes

• PS4: This variant has been reported in an individual with a personal or family history of an MH episode without a positive in vitro contracture test (IVCT) or caffeine halothane contracture test (CHCT) result, PS4 was not met (PMID:16732084).