The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • No CSPEC related information was provided by the message!

  • See Evidence submitted by expert panel for details.

Variant: NM_000540.2(RYR1):c.1453A>G (p.Met485Val)

CA024169

133076 (ClinVar)

Gene: RYR1
Condition: malignant hyperthermia, susceptibility to, 1
Inheritance Mode: Autosomal dominant inheritance
UUID: 7c0d5bd7-df13-45e4-8410-56684eecdbc7
Approved on: 2023-04-06
Published on: 2023-04-06

HGVS expressions

NM_000540.2:c.1453A>G
NM_000540.2(RYR1):c.1453A>G (p.Met485Val)
NC_000019.10:g.38455247A>G
CM000681.2:g.38455247A>G
NC_000019.9:g.38945887A>G
CM000681.1:g.38945887A>G
NC_000019.8:g.43637727A>G
NG_008866.1:g.26548A>G
ENST00000599547.6:n.1453A>G
ENST00000359596.8:c.1453A>G
ENST00000355481.8:c.1453A>G
ENST00000359596.7:n.1453A>G
ENST00000360985.7:c.1453A>G
NM_001042723.1:c.1453A>G
NM_000540.3:c.1453A>G
NM_001042723.2:c.1453A>G
NM_000540.3(RYR1):c.1453A>G (p.Met485Val)

Uncertain Significance

Met criteria codes 1
PM1
Not Met criteria codes 6
BA1 BS1 BP4 PS4 PS3 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 Methionine with Valine at codon 485 of the RYR1 protein, p.(Met485Val). The maximum allele frequency for this variant among the six major gnomAD populations is NFE: 0.00061, a frequency consistent with pathogenicity for MHS. This variant has been reported in individuals with central core disease and other myopathies inherited in a recessive pattern. No functional studies were identified for this variant that fulfilled the criteria for functional data as put forth by the ClinGen RYR1 VCEP for MHS (one study tested this variant in myotubes in the presence of other variants (PMID:16940308)). This variant resides in a region of RYR1 considered to be a hotspot for pathogenic variants that contribute to MHS, PM1 (PMID: 21118704). A REVEL score of 0.551 supports neither a pathogenic nor a benign status for this variant. This variant has been classified as a Variant of Unknown Significance. Criteria implemented: PM1.
Met criteria codes
PM1
N-terminal hotspot region.
Not Met criteria codes
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BP4
A REVEL score of 0.551 supports neither a pathogenic nor a benign status for this variant.
PS4
This variant has been reported in individuals with central core disease and other myopathies inherited in a recessive pattern.
PS3
No functional studies were identified for this variant that fulfilled the criteria for functional data as put forth by the ClinGen RYR1 VCEP for MHS (one study tested this variant in myotubes in the presence of other variants (PMID:16940308)).
PP3
A REVEL score of 0.551 supports neither a pathogenic nor a benign status for this variant.
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.