NM_000540.3(RYR1):c.1021G>A (p.Gly341Arg) AND RYR1-related disorder

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 22, 2025
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:: RCV000655541.17

Allele description [Variation Report for NM_000540.3(RYR1):c.1021G>A (p.Gly341Arg)]

NM_000540.3(RYR1):c.1021G>A (p.Gly341Arg)

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.1021G>A (p.Gly341Arg)

Other names:

NM_000540.3(RYR1):c.1021G>A

HGVS:

NC_000019.10:g.38448712G>A
NG_008866.1:g.20013G>A
NM_000540.3:c.1021G>AMANE SELECT
NM_001042723.2:c.1021G>A
NP_000531.2:p.Gly341Arg
NP_000531.2:p.Gly341Arg
NP_001036188.1:p.Gly341Arg
LRG_766t1:c.1021G>A
LRG_766:g.20013G>A
LRG_766p1:p.Gly341Arg
NC_000019.9:g.38939352G>A
NM_000540.2:c.1021G>A
P21817:p.Gly341Arg
p.(Gly341Arg)

Protein change:

G341R; GLY341ARG

Links:

UniProtKB: P21817#VAR_005592; OMIM: 180901.0006; dbSNP: rs121918592

NCBI 1000 Genomes Browser:

rs121918592

Molecular consequence:

NM_000540.3:c.1021G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001042723.2:c.1021G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000777472	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 22, 2025)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 8012359, 8825043, 19648156, 24433488, 9334205, 9873004, 12732639, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000777472

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 22, 2025)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Detection of a novel common mutation in the ryanodine receptor gene in malignant hyperthermia: implications for diagnosis and heterogeneity studies.

Quane KA, Keating KE, Manning BM, Healy JM, Monsieurs K, Heffron JJ, Lehane M, Heytens L, Krivosic-Horber R, Adnet P, et al.

Hum Mol Genet. 1994 Mar;3(3):471-6.

PubMed [citation]

PMID:: 8012359

Diagnosis of malignant hyperthermia: a comparison of the in vitro contracture test with the molecular genetic diagnosis in a large pedigree.

Healy JM, Quane KA, Keating KE, Lehane M, Heffron JJ, McCarthy TV.

J Med Genet. 1996 Jan;33(1):18-24.

PubMed [citation]

PMID:: 8825043
PMCID:: PMC1051806

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000777472.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 341 of the RYR1 protein (p.Gly341Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with malignant hyperthermia (PMID: 8012359, 8825043, 19648156, 24433488). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 12969). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on RYR1 protein function. Experimental studies have shown that this missense change affects RYR1 function (PMID: 9334205, 9873004, 12732639). For these reasons, this variant has been classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 16, 2025

ClinVar

Relating variation to medicine