The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

  • See Evidence submitted by expert panel for details.

Variant: NM_000540.2(RYR1):c.12881C>T (p.Thr4294Met)

CA024017

159834 (ClinVar)

Gene: RYR1
Condition: malignant hyperthermia, susceptibility to, 1
Inheritance Mode: Autosomal dominant inheritance
UUID: 13e778b6-fc1c-4a97-9c49-0878bad4f887

HGVS expressions

NM_000540.2:c.12881C>T
NM_000540.2(RYR1):c.12881C>T (p.Thr4294Met)
NC_000019.10:g.38565215C>T
CM000681.2:g.38565215C>T
NC_000019.9:g.39055855C>T
CM000681.1:g.39055855C>T
NC_000019.8:g.43747695C>T
NG_008866.1:g.136516C>T
ENST00000355481.8:c.12866C>T
ENST00000359596.7:n.12881C>T
ENST00000360985.7:c.12863C>T
NM_001042723.1:c.12866C>T
NM_000540.3:c.12881C>T
NM_001042723.2:c.12866C>T

Benign

Met criteria codes 1
BA1

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specifications for this VCEP
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 substitution of Threonine with Methionine at codon 4294 of the RYR1 protein, p.(Thr4294Met). The maximum allele frequency for this variant among the six major gnomAD populations is AFR: 0.0193, which is considered to be too common for a pathogenic variant causing autosomal dominantly inherited MHS, BA1. This variant has been classified as Benign. Criteria implemented: BA1.
Met criteria codes
BA1
MAF > 0.0038 in AFR population.
Approved on: 2021-03-17
Published on: 2021-03-31
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