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NM_000540.3(RYR1):c.11993TGA[2] (p.Met4000del) AND Malignant hyperthermia, susceptibility to, 1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 28, 2023
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:
RCV004011029.2

Allele description [Variation Report for NM_000540.3(RYR1):c.11993TGA[2] (p.Met4000del)]

NM_000540.3(RYR1):c.11993TGA[2] (p.Met4000del)

Gene:
RYR1:ryanodine receptor 1 [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
19q13.2
Genomic location:
Preferred name:
NM_000540.3(RYR1):c.11993TGA[2] (p.Met4000del)
HGVS:
  • NC_000019.10:g.38543856TGA[2]
  • NC_000019.9:g.39034502_39034504del
  • NG_008866.1:g.115157TGA[2]
  • NM_000540.3:c.11993TGA[2]MANE SELECT
  • NM_001042723.2:c.11978TGA[2]
  • NP_000531.2:p.Met4000del
  • NP_001036188.1:p.Met3995del
  • LRG_766:g.115157TGA[2]
  • NC_000019.9:g.39034495_39034497del
  • NC_000019.9:g.39034496TGA[2]
  • NC_000019.9:g.39034502_39034504del
Protein change:
M3995del
Links:
dbSNP: rs2145776584
NCBI 1000 Genomes Browser:
rs2145776584
Molecular consequence:
  • NM_000540.3:c.11993TGA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
  • NM_001042723.2:c.11978TGA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
Observations:
1

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
SCV004828057All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Aug 28, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided108544not providedclinical testing

Citations

PubMed

'Dusty core disease' (DuCD): expanding morphological spectrum of RYR1 recessive myopathies.

Garibaldi M, Rendu J, Brocard J, Lacene E, Fauré J, Brochier G, Beuvin M, Labasse C, Madelaine A, Malfatti E, Bevilacqua JA, Lubieniecki F, Monges S, Taratuto AL, Laporte J, Marty I, Antonini G, Romero NB.

Acta Neuropathol Commun. 2019 Jan 5;7(1):3. doi: 10.1186/s40478-018-0655-5.

PubMed [citation]
PMID:
30611313
PMCID:
PMC6320585

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, SCV004828057.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

This variant results in the in-frame deletion of one amino acid in the RYR1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with autosomal dominant malignant hyperthermia in the literature, although it is associated with other phenotype(s) (ClinVar variation ID: 1473663; PMID: 30611313) This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Due to insufficient evidence, this variant is classified as a Variant of Uncertain Significance for autosomal dominant malignant hyperthermia.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown108544not providednot provided1not providednot providednot provided

Last Updated: Sep 29, 2024