U.S. flag

An official website of the United States government

NM_000540.3(RYR1):c.5340dup (p.Cys1781fs) AND Malignant hyperthermia, susceptibility to, 1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 5, 2022
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:
RCV004000148.2

Allele description [Variation Report for NM_000540.3(RYR1):c.5340dup (p.Cys1781fs)]

NM_000540.3(RYR1):c.5340dup (p.Cys1781fs)

Gene:
RYR1:ryanodine receptor 1 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
19q13.2
Genomic location:
Preferred name:
NM_000540.3(RYR1):c.5340dup (p.Cys1781fs)
HGVS:
  • NC_000019.10:g.38485995dup
  • NG_008866.1:g.57296dup
  • NM_000540.3:c.5340dupMANE SELECT
  • NM_001042723.2:c.5340dup
  • NP_000531.2:p.Cys1781fs
  • NP_001036188.1:p.Cys1781fs
  • LRG_766t1:c.5340dup
  • LRG_766:g.57296dup
  • NC_000019.9:g.38976629_38976630insC
  • NC_000019.9:g.38976635dup
  • NC_000019.9:g.38976635dup
  • NM_000540.2:c.5340dup
Protein change:
C1781fs
Links:
dbSNP: rs1969271215
NCBI 1000 Genomes Browser:
rs1969271215
Molecular consequence:
  • NM_000540.3:c.5340dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001042723.2:c.5340dup - frameshift variant - [Sequence Ontology: SO:0001589]
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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004820854All of Us Research Program, National Institutes of Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain Significance
(Dec 5, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not 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, SCV004820854.1

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

Description

This pathogenicity assessment is for autosomal dominant malignant hyperthermia susceptibility phenotype. This frameshift variant is predicted to result in an absent RYR1 protein product. Loss of RYR1 function due to haploinsufficiency is associated with congenital myopathy (https://clinicalgenome.org/), but it is not an established disease mechanism for autosomal dominant malignant hyperthermia susceptibility. Therefore, this variant is classified as a Variant of Uncertain Significance for malignant hyperthermia susceptibility.

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

Last Updated: Sep 29, 2024