U.S. flag

An official website of the United States government

NM_000540.3(RYR1):c.14364+1G>T AND Malignant hyperthermia of anesthesia

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 3, 2022
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001803463.1

Allele description [Variation Report for NM_000540.3(RYR1):c.14364+1G>T]

NM_000540.3(RYR1):c.14364+1G>T

Gene:
RYR1:ryanodine receptor 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19q13.2
Genomic location:
Preferred name:
NM_000540.3(RYR1):c.14364+1G>T
HGVS:
  • NC_000019.10:g.38578205G>T
  • NG_008866.1:g.149506G>T
  • NM_000540.3:c.14364+1G>TMANE SELECT
  • NM_001042723.2:c.14349+1G>T
  • LRG_766:g.149506G>T
  • NC_000019.9:g.39068845G>T
Links:
dbSNP: rs1974046221
NCBI 1000 Genomes Browser:
rs1974046221
Molecular consequence:
  • NM_000540.3:c.14364+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001042723.2:c.14349+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Malignant hyperthermia of anesthesia
Synonyms:
Hyperthermia of anesthesia; Anesthesic-triggered malignant hyperthermia
Identifiers:
MONDO: MONDO:0018493; MedGen: C0024591; Human Phenotype Ontology: HP:0034733

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002047654ClinGen Malignant Hyperthermia Susceptibility Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen MHS ACMG Specifications V1)
Uncertain significance
(Jan 3, 2022)
germlinecuration

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Malignant Hyperthermia Susceptibility Variant Curation Expert Panel, ClinGen, SCV002047654.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

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 guanine with thymine at position 14364+1 of the RYR1 cDNA, c.14364+1G>T. 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 and a positive in vitro contracture test (IVCT) or caffeine halothane contracture test (CHCT) result (if the proband was unavailable for testing, a positive diagnostic test result in a mutation-positive relative was counted), PS4_Supporting (PMID: 25960145). No functional studies were identified for this variant. This variant does not reside in a hotspot for pathogenic variants that contribute to MHS. This variant is predicted to disrupt splicing, however, loss of function of RYR1 is not a common molecular etiology for MHS. This variant has been classified as a Variant of Unknown Significance. Criteria implemented: PS4_Supporting.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 16, 2024