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Variant: NM_000540.3(RYR1):c.8290G>A (p.Glu2764Lys)

CA024903

133221 (ClinVar)

Gene: RYR1
Condition: malignant hyperthermia of anesthesia
Inheritance Mode: Autosomal dominant inheritance
UUID: 57514f04-58e4-4752-8707-d6f8f7d5954e
Approved on: 2023-04-06
Published on: 2023-04-06

HGVS expressions

NM_000540.3:c.8290G>A
NM_000540.3(RYR1):c.8290G>A (p.Glu2764Lys)
NC_000019.10:g.38505061G>A
CM000681.2:g.38505061G>A
NC_000019.9:g.38995701G>A
CM000681.1:g.38995701G>A
NC_000019.8:g.43687541G>A
NG_008866.1:g.76362G>A
ENST00000599547.6:n.8290G>A
ENST00000359596.8:c.8290G>A
ENST00000355481.8:c.8290G>A
ENST00000359596.7:n.8290G>A
ENST00000360985.7:c.8287G>A
ENST00000594335.5:n.1742G>A
NM_000540.2:c.8290G>A
NM_001042723.1:c.8290G>A
NM_001042723.2:c.8290G>A
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Uncertain Significance

The Expert Panel has overridden the computationally generated classification - "[unknown]"
Not Met criteria codes 4
PM1 BP4 PS4 PP3

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 glutamic acid with lysine at codon 2764 of the RYR1 protein, p.(Glu2764Lys). The maximum allele frequency for this variant among the six major gnomAD populations is EAS: 0.000109, a frequency consistent with pathogenicity for MHS. To our knowledge, this variant has not been reported in any individuals with a personal or family history of an MH episode and a positive in vitro contracture test (IVCT) or caffeine halothane contracture test (CHCT). No functional studies were identified for this variant. This variant does not reside in a hotspot for pathogenic variants that contribute to MHS. A REVEL score of 0.842 supports neither a pathogenic nor a benign status for this variant. This variant has been classified as a Variant of Unknown Significance. No criteria implemented.
Not Met criteria codes
PM1
This variant does not reside in a hotspot for pathogenic variants that contribute to MHS.
BP4
A REVEL score of 0.842 supports neither a pathogenic nor a benign status for this variant.
PS4
To our knowledge, this variant has not been reported in any individuals with a personal or family history of an MH episode and a positive in vitro contracture test (IVCT) or caffeine halothane contracture test (CHCT).
PP3
A REVEL score of 0.842 supports neither a pathogenic nor a benign status for this variant.
Curation History
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