NM_000540.3(RYR1):c.7028-10G>A AND Malignant hyperthermia, susceptibility to, 1

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 21, 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:: RCV003514371.1

Allele description [Variation Report for NM_000540.3(RYR1):c.7028-10G>A]

NM_000540.3(RYR1):c.7028-10G>A

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.7028-10G>A

HGVS:

NC_000019.10:g.38499625G>A
NG_008866.1:g.70926G>A
NM_000540.3:c.7028-10G>AMANE SELECT
NM_001042723.2:c.7028-10G>A
LRG_766t1:c.7028-10G>A
LRG_766:g.70926G>A
NC_000019.9:g.38990265G>A
NM_000540.2:c.7028-10G>A

Links:

dbSNP: rs1005260620

NCBI 1000 Genomes Browser:

rs1005260620

Molecular consequence:

NM_000540.3:c.7028-10G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001042723.2:c.7028-10G>A - intron variant - [Sequence Ontology: SO:0001627]

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
SCV004358115	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 21, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 31559918, 32236737, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004358115

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 21, 2023)

germline

clinical testing

PubMed (3)
[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

Bayesian modeling to predict malignant hyperthermia susceptibility and pathogenicity of RYR1, CACNA1S and STAC3 variants.

Sadhasivam S, Brandom BW, Henker RA, McAuliffe JJ.

Pharmacogenomics. 2019 Sep;20(14):989-1003. doi: 10.2217/pgs-2019-0055.

PubMed [citation]

PMID:: 31559918
PMCID:: PMC7006767

Intracellular calcium leak as a therapeutic target for RYR1-related myopathies.

Kushnir A, Todd JJ, Witherspoon JW, Yuan Q, Reiken S, Lin H, Munce RH, Wajsberg B, Melville Z, Clarke OB, Wedderburn-Pugh K, Wronska A, Razaqyar MS, Chrismer IC, Shelton MO, Mankodi A, Grunseich C, Tarnopolsky MA, Tanji K, Hirano M, Riazi S, Kraeva N, et al.

Acta Neuropathol. 2020 Jun;139(6):1089-1104. doi: 10.1007/s00401-020-02150-w. Epub 2020 Mar 31.

PubMed [citation]

PMID:: 32236737
PMCID:: PMC7788518

See all PubMed Citations (3)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV004358115.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant causes a G to A nucleotide substitution at the -10 position of intron 43/105 of the RYR1 gene. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual who carried two other variants in the genes associated with malignant hyperthermia susceptibility (PMID: 31559918) and in an individual affected with myopathy (PMID: 32236737). This variant has been identified in 5/268194 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: Sep 29, 2024

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