NM_000540.3(RYR1):c.14204G>A (p.Arg4735Gln) AND Malignant hyperthermia, susceptibility to, 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 9, 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:: RCV003514535.1

Allele description [Variation Report for NM_000540.3(RYR1):c.14204G>A (p.Arg4735Gln)]

NM_000540.3(RYR1):c.14204G>A (p.Arg4735Gln)

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.14204G>A (p.Arg4735Gln)

HGVS:

NC_000019.10:g.38577949G>A
NG_008866.1:g.149250G>A
NM_000540.3:c.14204G>AMANE SELECT
NM_001042723.2:c.14189G>A
NP_000531.2:p.Arg4735Gln
NP_001036188.1:p.Arg4730Gln
LRG_766:g.149250G>A
NC_000019.9:g.39068589G>A

Protein change:

R4730Q

Links:

dbSNP: rs754190031

NCBI 1000 Genomes Browser:

rs754190031

Molecular consequence:

NM_000540.3:c.14204G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001042723.2:c.14189G>A - missense variant - [Sequence Ontology: SO:0001583]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004358221	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 9, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24433488, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004358221

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 9, 2023)

germline

clinical testing

PubMed (2)
[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

Functional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study.

Klingler W, Heiderich S, Girard T, Gravino E, Heffron JJ, Johannsen S, Jurkat-Rott K, Rüffert H, Schuster F, Snoeck M, Sorrentino V, Tegazzin V, Lehmann-Horn F.

Orphanet J Rare Dis. 2014 Jan 16;9:8. doi: 10.1186/1750-1172-9-8.

PubMed [citation]

PMID:: 24433488
PMCID:: PMC3896768

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 Color Diagnostics, LLC DBA Color Health, SCV004358221.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This missense variant replaces arginine with glutamine at codon 4735 of the RYR1 protein. Computational prediction tool indicates that this variant may have a neutral impact on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with malignant hyperthermia susceptibility (PMID: 24433488). This variant has been identified in 2/251402 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	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: Oct 20, 2024

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