NM_000540.3(RYR1):c.13934G>A (p.Arg4645Gln) AND not provided

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Feb 23, 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:: RCV000119491.8

Allele description [Variation Report for NM_000540.3(RYR1):c.13934G>A (p.Arg4645Gln)]

NM_000540.3(RYR1):c.13934G>A (p.Arg4645Gln)

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.13934G>A (p.Arg4645Gln)

HGVS:

NC_000019.10:g.38572206G>A
NG_008866.1:g.143507G>A
NM_000540.3:c.13934G>AMANE SELECT
NM_001042723.2:c.13919G>A
NP_000531.2:p.Arg4645Gln
NP_000531.2:p.Arg4645Gln
NP_001036188.1:p.Arg4640Gln
LRG_766t1:c.13934G>A
LRG_766:g.143507G>A
LRG_766p1:p.Arg4645Gln
NC_000019.9:g.39062846G>A
NM_000540.2:c.13934G>A
NM_000540.3(RYR1):c.13934G>AMANE SELECT
p.(Arg4645Gln)

Protein change:

R4640Q

Links:

dbSNP: rs193922860

NCBI 1000 Genomes Browser:

rs193922860

Molecular consequence:

NM_000540.3:c.13934G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001042723.2:c.13919G>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
SCV000154398	Leiden Muscular Dystrophy (RYR1)	no classification provided	not provided	unknown	not provided	PubMed (2) [See all records that cite these PMIDs] 16917943, 16732084
SCV001821047	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Dec 30, 2020)	germline	clinical testing	Citation Link,
SCV003820579	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 23, 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

SCV000154398

Leiden Muscular Dystrophy (RYR1)

no classification provided

not provided

unknown

not provided

PubMed (2)
[See all records that cite these PMIDs]

SCV001821047

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Dec 30, 2020)

germline

clinical testing

Citation Link,

SCV003820579

Revvity Omics, Revvity

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 23, 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	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
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Malignant hyperthermia in Japan: mutation screening of the entire ryanodine receptor type 1 gene coding region by direct sequencing.

Ibarra M CA, Wu S, Murayama K, Minami N, Ichihara Y, Kikuchi H, Noguchi S, Hayashi YK, Ochiai R, Nishino I.

Anesthesiology. 2006 Jun;104(6):1146-54.

PubMed [citation]

PMID:: 16732084

See all PubMed Citations (3)

Details of each submission

From Leiden Muscular Dystrophy (RYR1), SCV000154398.1

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

#	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, SCV001821047.1

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

Description

Identified as heterozygous in an individual with neuroleptic malignant syndrome, however it was also identified in multiple control samples (Sato et al., 2010); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21918424, 19223216, 16917943, 21878807, 23476141, 19931341, 16732084)

#	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

From Revvity Omics, Revvity, SCV003820579.2

#	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

Last Updated: Nov 3, 2024

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