U.S. flag

An official website of the United States government

NM_000540.3(RYR1):c.6710G>A (p.Cys2237Tyr) AND RYR1-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 26, 2021
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:
RCV001871976.12

Allele description [Variation Report for NM_000540.3(RYR1):c.6710G>A (p.Cys2237Tyr)]

NM_000540.3(RYR1):c.6710G>A (p.Cys2237Tyr)

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.6710G>A (p.Cys2237Tyr)
HGVS:
  • NC_000019.10:g.38496455G>A
  • NG_008866.1:g.67756G>A
  • NM_000540.3:c.6710G>AMANE SELECT
  • NM_001042723.2:c.6710G>A
  • NP_000531.2:p.Cys2237Tyr
  • NP_001036188.1:p.Cys2237Tyr
  • LRG_766t1:c.6710G>A
  • LRG_766:g.67756G>A
  • NC_000019.9:g.38987095G>A
  • NC_000019.9:g.38987095G>A
  • NM_000540.2:c.6710G>A
Protein change:
C2237Y
Links:
dbSNP: rs2145586397
NCBI 1000 Genomes Browser:
rs2145586397
Molecular consequence:
  • NM_000540.3:c.6710G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042723.2:c.6710G>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

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002173505Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Aug 26, 2021) 		germlineclinical testing

PubMed (2)
[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

RYR1-related myopathies: a wide spectrum of phenotypes throughout life.

Snoeck M, van Engelen BG, Küsters B, Lammens M, Meijer R, Molenaar JP, Raaphorst J, Verschuuren-Bemelmans CC, Straathof CS, Sie LT, de Coo IF, van der Pol WL, de Visser M, Scheffer H, Treves S, Jungbluth H, Voermans NC, Kamsteeg EJ.

Eur J Neurol. 2015 Jul;22(7):1094-112. doi: 10.1111/ene.12713. Epub 2015 May 11.

PubMed [citation]
PMID:
25960145

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002173505.3

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

Description

For these reasons, this variant has been classified as Pathogenic. 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. This missense change has been observed in individual(s) with malignant hyperthermia susceptibility (PMID: 25960145). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 2237 of the RYR1 protein (p.Cys2237Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine.

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

Last Updated: Oct 26, 2024