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NM_000540.3(RYR1):c.131G>A (p.Arg44His) AND RYR1-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 22, 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:
RCV000531069.5

Allele description [Variation Report for NM_000540.3(RYR1):c.131G>A (p.Arg44His)]

NM_000540.3(RYR1):c.131G>A (p.Arg44His)

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.131G>A (p.Arg44His)
Other names:
NM_000540.2(RYR1):c.131G>A
HGVS:
  • NC_000019.10:g.38440830G>A
  • NG_008866.1:g.12131G>A
  • NM_000540.3:c.131G>AMANE SELECT
  • NM_001042723.2:c.131G>A
  • NP_000531.2:p.Arg44His
  • NP_000531.2:p.Arg44His
  • NP_001036188.1:p.Arg44His
  • LRG_766t1:c.131G>A
  • LRG_766:g.12131G>A
  • LRG_766p1:p.Arg44His
  • NC_000019.9:g.38931470G>A
  • NC_000019.9:g.38931470G>A
  • NM_000540.2:c.131G>A
  • p.(Arg44His)
Protein change:
R44H
Links:
dbSNP: rs139161723
NCBI 1000 Genomes Browser:
rs139161723
Molecular consequence:
  • NM_000540.3:c.131G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042723.2:c.131G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
RYR1-related disorder
Synonyms:
RYR1-Related Disorders; RYR1-related condition
Identifiers:
MedGen: CN239331

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000659808Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jan 22, 2024) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Frequency and localization of mutations in the 106 exons of the RYR1 gene in 50 individuals with malignant hyperthermia.

Galli L, Orrico A, Lorenzini S, Censini S, Falciani M, Covacci A, Tegazzin V, Sorrentino V.

Hum Mutat. 2006 Aug;27(8):830.

PubMed [citation]
PMID:
16835904

Mutations in RYR1 in malignant hyperthermia and central core disease.

Robinson R, Carpenter D, Shaw MA, Halsall J, Hopkins P.

Hum Mutat. 2006 Oct;27(10):977-89. Review.

PubMed [citation]
PMID:
16917943
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000659808.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 44 of the RYR1 protein (p.Arg44His). This variant is present in population databases (rs139161723, gnomAD 0.007%). This missense change has been observed in individuals with autosomal dominant malignant hyperthermia (PMID: 16835904, 16917943; Invitae). This variant has been reported in individual(s) with autosomal recessive congenital myopathy (Invitae); however, the role of the variant in this condition is currently unclear. ClinVar contains an entry for this variant (Variation ID: 133046). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt RYR1 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 16, 2024