NM_000540.3(RYR1):c.5427C>G (p.Asp1809Glu) AND Malignant hyperthermia, susceptibility to, 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 4, 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:: RCV004013173.2

Allele description [Variation Report for NM_000540.3(RYR1):c.5427C>G (p.Asp1809Glu)]

NM_000540.3(RYR1):c.5427C>G (p.Asp1809Glu)

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.5427C>G (p.Asp1809Glu)

HGVS:

NC_000019.10:g.38486082C>G
NG_008866.1:g.57383C>G
NM_000540.3:c.5427C>GMANE SELECT
NM_001042723.2:c.5427C>G
NP_000531.2:p.Asp1809Glu
NP_000531.2:p.Asp1809Glu
NP_001036188.1:p.Asp1809Glu
LRG_766t1:c.5427C>G
LRG_766:g.57383C>G
LRG_766p1:p.Asp1809Glu
NC_000019.9:g.38976722C>G
NM_000540.2:c.5427C>G

Protein change:

D1809E

Molecular consequence:

NM_000540.3:c.5427C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001042723.2:c.5427C>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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

Recent activity

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nuclear pore complex protein Nup205 [Rattus norvegicus]
nuclear pore complex protein Nup205 [Rattus norvegicus]
gi|157820537|ref|NP_001102090.1|

Protein
Genome-wide chromatin profiles of PBRM1 Drug treatment [RNA-Seq]
Genome-wide chromatin profiles of PBRM1 Drug treatment [RNA-Seq]
Genome-wide chromatin profiles of PBRM1 Drug treatment [RNA-Seq]

BioProject
PREDICTED: Mus musculus prominin 1 (Prom1), transcript variant X19, mRNA
PREDICTED: Mus musculus prominin 1 (Prom1), transcript variant X19, mRNA
gi|1907161198|ref|XM_006503789.3|

Nucleotide
Adprhl1 ADP-ribosylhydrolase like 1 [Mus musculus]
Adprhl1 ADP-ribosylhydrolase like 1 [Mus musculus]
Gene ID:234072

Gene
234072[uid] AND (alive[prop]) (1)
Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004832436	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (May 4, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004832436

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(May 4, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

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 All of Us Research Program, National Institutes of Health, SCV004832436.1

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

Description

This missense variant replaces aspartic acid with glutamic acid at codon 1809 of the RYR1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RYR1-related disorders in the literature. This variant has been identified in 2/240412 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	108544	not provided	not provided		1	not provided	not provided	not provided

Last Updated: May 7, 2024

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