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NM_000540.3(RYR1):c.652G>A (p.Val218Ile) AND RYR1-related disorder

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 18, 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:
RCV002514603.2

Allele description [Variation Report for NM_000540.3(RYR1):c.652G>A (p.Val218Ile)]

NM_000540.3(RYR1):c.652G>A (p.Val218Ile)

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.652G>A (p.Val218Ile)
Other names:
NM_000540.2(RYR1):c.652G>A; p.Val218Ile
HGVS:
  • NC_000019.10:g.38446492G>A
  • NG_008866.1:g.17793G>A
  • NM_000540.3:c.652G>AMANE SELECT
  • NM_001042723.2:c.652G>A
  • NP_000531.2:p.Val218Ile
  • NP_000531.2:p.Val218Ile
  • NP_001036188.1:p.Val218Ile
  • LRG_766t1:c.652G>A
  • LRG_766:g.17793G>A
  • LRG_766p1:p.Val218Ile
  • NC_000019.9:g.38937132G>A
  • NC_000019.9:g.38937132G>A
  • NM_000540.2:c.652G>A
  • p.(Val218Ile)
Protein change:
V218I
Links:
dbSNP: rs193922759
NCBI 1000 Genomes Browser:
rs193922759
Molecular consequence:
  • NM_000540.3:c.652G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042723.2:c.652G>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
SCV003447675Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 18, 2023) 		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

Malignant hyperthermia in Japan: mutation screening of the entire ryanodine receptor type 1 gene coding region by direct sequencing.

Ibarra M CA, Wu S, Murayama K, Minami N, Ichihara Y, Kikuchi H, Noguchi S, Hayashi YK, Ochiai R, Nishino I.

Anesthesiology. 2006 Jun;104(6):1146-54.

PubMed [citation]
PMID:
16732084

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, SCV003447675.2

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

Description

This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 218 of the RYR1 protein (p.Val218Ile). This variant is present in population databases (rs193922759, gnomAD 0.002%). This missense change has been observed in individual(s) with malignant hyperthermia susceptibility (PMID: 16732084, 16917943). ClinVar contains an entry for this variant (Variation ID: 133160). 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) has been performed at Invitae 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Jul 23, 2024