NM_000540.3(RYR1):c.7523G>A (p.Arg2508His) AND not provided

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Jun 16, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000119719.21

Allele description [Variation Report for NM_000540.3(RYR1):c.7523G>A (p.Arg2508His)]

NM_000540.3(RYR1):c.7523G>A (p.Arg2508His)

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.7523G>A (p.Arg2508His)

Other names:

NM_000540.3(RYR1):c.7523G>A; p.Arg2508His

HGVS:

NC_000019.10:g.38500899G>A
NG_008866.1:g.72200G>A
NM_000540.3:c.7523G>AMANE SELECT
NM_001042723.2:c.7523G>A
NP_000531.2:p.Arg2508His
NP_000531.2:p.Arg2508His
NP_001036188.1:p.Arg2508His
LRG_766t1:c.7523G>A
LRG_766:g.72200G>A
LRG_766p1:p.Arg2508His
NC_000019.9:g.38991539G>A
NM_000540.2:c.7523G>A
p.(Arg2508His)

Protein change:

R2508H

Links:

PharmGKB: 1447673778PA164749136; PharmGKB: 1447673778PA449461; PharmGKB: 1447673778PA449845; PharmGKB: 1447673778PA450106; PharmGKB: 1447673778PA450434; PharmGKB: 1447673778PA451341; PharmGKB: 1447673778PA451522; dbSNP: rs193922818

NCBI 1000 Genomes Browser:

rs193922818

Molecular consequence:

NM_000540.3:c.7523G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001042723.2:c.7523G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000154626	Leiden Muscular Dystrophy (RYR1)	no classification provided	not provided	unknown	not provided	PubMed (3) [See all records that cite these PMIDs] 21282829, 16917943, 16732084
SCV000852781	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 20, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001446515	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 23, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002019972	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 28, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003933429	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 16, 2023)	germline	clinical testing	Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Chan B, Chen SP, Wong WC, Mak CM, Wong S, Chan KY, Chan AY.

Hong Kong Med J. 2011 Feb;17(1):67-70.

PubMed [citation]

PMID:: 21282829

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 (4)

Details of each submission

From Leiden Muscular Dystrophy (RYR1), SCV000154626.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	not provided	1	not provided	not provided		not provided	not provided	not provided	not provided

From PreventionGenetics, part of Exact Sciences, SCV000852781.1

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

#	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

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001446515.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV002019972.3

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

#	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

From GeneDx, SCV003933429.1

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

Description

Published functional studies demonstrate a damaging effect on calcium homeostasis (Miyoshi et al., 2015); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34850017, 21282829, 16917943, 16835904, 25960145, 23558838, 27586648, 30236257, 31127727, 32528171, 17483490, 32381727, 16732084, 35428369, 26381711, 16621918)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 23, 2024

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