NM_000540.3(RYR1):c.11993TGA[2] (p.Met4000del) AND Malignant hyperthermia, susceptibility to, 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 28, 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:: RCV004011029.2

Allele description [Variation Report for NM_000540.3(RYR1):c.11993TGA[2] (p.Met4000del)]

NM_000540.3(RYR1):c.11993TGA[2] (p.Met4000del)

Gene:

RYR1:ryanodine receptor 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

19q13.2

Genomic location:

Preferred name:

NM_000540.3(RYR1):c.11993TGA[2] (p.Met4000del)

HGVS:

NC_000019.10:g.38543856TGA[2]
NC_000019.9:g.39034502_39034504del
NG_008866.1:g.115157TGA[2]
NM_000540.3:c.11993TGA[2]MANE SELECT
NM_001042723.2:c.11978TGA[2]
NP_000531.2:p.Met4000del
NP_001036188.1:p.Met3995del
LRG_766:g.115157TGA[2]
NC_000019.9:g.39034495_39034497del
NC_000019.9:g.39034496TGA[2]
NC_000019.9:g.39034502_39034504del

Protein change:

M3995del

Links:

dbSNP: rs2145776584

NCBI 1000 Genomes Browser:

rs2145776584

Molecular consequence:

NM_000540.3:c.11993TGA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001042723.2:c.11978TGA[2] - inframe_deletion - [Sequence Ontology: SO:0001822]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004828057	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Aug 28, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30611313, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004828057

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Aug 28, 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	1	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

'Dusty core disease' (DuCD): expanding morphological spectrum of RYR1 recessive myopathies.

Garibaldi M, Rendu J, Brocard J, Lacene E, Fauré J, Brochier G, Beuvin M, Labasse C, Madelaine A, Malfatti E, Bevilacqua JA, Lubieniecki F, Monges S, Taratuto AL, Laporte J, Marty I, Antonini G, Romero NB.

Acta Neuropathol Commun. 2019 Jan 5;7(1):3. doi: 10.1186/s40478-018-0655-5.

PubMed [citation]

PMID:: 30611313
PMCID:: PMC6320585

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, SCV004828057.1

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

Description

This variant results in the in-frame deletion of one amino acid in the RYR1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with autosomal dominant malignant hyperthermia in the literature, although it is associated with other phenotype(s) (ClinVar variation ID: 1473663; PMID: 30611313) This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Due to insufficient evidence, this variant is classified as a Variant of Uncertain Significance for autosomal dominant malignant hyperthermia.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine