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Variant: NM_000540.2(RYR1):c.4400A>G (p.Lys1467Arg)

CA024439

161371 (ClinVar)

Gene: RYR1
Condition: malignant hyperthermia, susceptibility to, 1
Inheritance Mode: Autosomal dominant inheritance
UUID: 40ad2c20-84b2-413d-80d7-399ec3761d39

HGVS expressions

NM_000540.2:c.4400A>G
NM_000540.2(RYR1):c.4400A>G (p.Lys1467Arg)
NC_000019.10:g.38477816A>G
CM000681.2:g.38477816A>G
NC_000019.9:g.38968456A>G
CM000681.1:g.38968456A>G
NC_000019.8:g.43660296A>G
NG_008866.1:g.49117A>G
ENST00000599547.6:n.4400A>G
ENST00000359596.8:c.4400A>G
ENST00000355481.8:c.4400A>G
ENST00000359596.7:n.4400A>G
ENST00000360985.7:c.4397A>G
NM_001042723.1:c.4400A>G
NM_000540.3:c.4400A>G
NM_001042723.2:c.4400A>G
NM_000540.3(RYR1):c.4400A>G (p.Lys1467Arg)

Uncertain Significance

Met criteria codes 1
BP4
Not Met criteria codes 2
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 Lysine with Arginine at codon 1467 of the RYR1 protein, p.(Lys1467Arg). This variant was not present in a large population database (gnomAD) at the time this variant was interpreted. To our knowledge, this variant has not been reported in individuals with a personal or family history of an MH episode. 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 <0.5 supports a benign status for this variant, BP4. This variant has been classified as a Variant of Unknown Significance. Criteria implemented: BP4.
Met criteria codes
BP4
REVEL < 0.50
Not Met criteria codes
PS4
Reported in one individual with hyperCKemia.
PP3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Approved on: 2023-04-06
Published on: 2023-04-06
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