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NM_000540.3(RYR1):c.7039G>A (p.Glu2347Lys) AND Malignant hyperthermia, susceptibility to, 1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 11, 2024
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV004011112.2

Allele description [Variation Report for NM_000540.3(RYR1):c.7039G>A (p.Glu2347Lys)]

NM_000540.3(RYR1):c.7039G>A (p.Glu2347Lys)

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.7039G>A (p.Glu2347Lys)
HGVS:
  • NC_000019.10:g.38499646G>A
  • NG_008866.1:g.70947G>A
  • NM_000540.3:c.7039G>AMANE SELECT
  • NM_001042723.2:c.7039G>A
  • NP_000531.2:p.Glu2347Lys
  • NP_001036188.1:p.Glu2347Lys
  • LRG_766:g.70947G>A
  • NC_000019.9:g.38990286G>A
Protein change:
E2347K
Links:
dbSNP: rs750951875
NCBI 1000 Genomes Browser:
rs750951875
Molecular consequence:
  • NM_000540.3:c.7039G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042723.2:c.7039G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

Condition(s)

Name:
Malignant hyperthermia, susceptibility to, 1 (MHS1)
Synonyms:
Anesthesia related hyperthermia; Malignant hyperpyrexia; Fulminating hyperpyrexia; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007783; MedGen: C2930980; Orphanet: 423; OMIM: 145600

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004837790All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Jan 11, 2024) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown2not providednot provided108544not providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004837790.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (1)

Description

This missense variant replaces glutamic acid with lysine at codon 2347 of the RYR1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RYR1-related disorders in the literature. This variant has been identified in 9/238760 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided2not providednot providednot provided

Last Updated: Sep 29, 2024