NM_000540.3(RYR1):c.7304G>T (p.Arg2435Leu) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 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:: RCV000119700.1

Allele description [Variation Report for NM_000540.3(RYR1):c.7304G>T (p.Arg2435Leu)]

NM_000540.3(RYR1):c.7304G>T (p.Arg2435Leu)

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.7304G>T (p.Arg2435Leu)

Other names:

NM_000540.2(RYR1):c.7304G>T

HGVS:

NC_000019.10:g.38499997G>T
NG_008866.1:g.71298G>T
NM_000540.3:c.7304G>TMANE SELECT
NM_001042723.2:c.7304G>T
NP_000531.2:p.Arg2435Leu
NP_000531.2:p.Arg2435Leu
NP_001036188.1:p.Arg2435Leu
LRG_766t1:c.7304G>T
LRG_766:g.71298G>T
LRG_766p1:p.Arg2435Leu
NC_000019.9:g.38990637G>T
NM_000540.2:c.7304G>T
P21817:p.Arg2435Leu
p.(Arg2435Leu)

Protein change:

R2435L

Links:

UniProtKB: P21817#VAR_008974; dbSNP: rs28933396

NCBI 1000 Genomes Browser:

rs28933396

Molecular consequence:

NM_000540.3:c.7304G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001042723.2:c.7304G>T - 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
SCV000154607	Leiden Muscular Dystrophy (RYR1)	no classification provided	not provided	unknown	not provided	PubMed (3) [See all records that cite these PMIDs] 16835904, 16917943, 17483490
SCV004036242	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Mar 21, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000154607

Leiden Muscular Dystrophy (RYR1)

no classification provided

not provided

unknown

not provided

PubMed (3)
[See all records that cite these PMIDs]

SCV004036242

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Mar 21, 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	not provided	not provided	clinical testing
not provided	unknown	not provided	not provided	not provided	not provided	1	not provided	literature only

Citations

PubMed

Frequency and localization of mutations in the 106 exons of the RYR1 gene in 50 individuals with malignant hyperthermia.

Galli L, Orrico A, Lorenzini S, Censini S, Falciani M, Covacci A, Tegazzin V, Sorrentino V.

Hum Mutat. 2006 Aug;27(8):830.

PubMed [citation]

PMID:: 16835904

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 (3)

Details of each submission

From Leiden Muscular Dystrophy (RYR1), SCV000154607.1

#	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 GeneDx, SCV004036242.1

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

Description

Identified in the heterozygous state in affected members of a family with central core disease; but it is unknown whether these individuals were screened for variants in other genes associated with myopathy (PMID: 23183335); Published functional studies demonstrate the variant results in increased calcium channel activity (PMIID: 28687594); 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: 10051009, 12668474, 28687594, 19513315, 15347586, 19027160, 25214167, 23558838, 17483490, 32528171, 16835904, 16917943, 12208234, 12709367, 23183335)

#	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: Sep 29, 2024

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