NM_000540.3(RYR1):c.14581C>T (p.Arg4861Cys) AND not provided

Germline classification:: Pathogenic (7 submissions)
Last evaluated:: Jun 26, 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:: RCV000119532.17

Allele description [Variation Report for NM_000540.3(RYR1):c.14581C>T (p.Arg4861Cys)]

NM_000540.3(RYR1):c.14581C>T (p.Arg4861Cys)

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.14581C>T (p.Arg4861Cys)

Other names:

NM_000540.2(RYR1):c.14581C>T

HGVS:

NC_000019.10:g.38580439C>T
NG_008866.1:g.151740C>T
NM_000540.3:c.14581C>TMANE SELECT
NM_001042723.2:c.14566C>T
NP_000531.2:p.Arg4861Cys
NP_000531.2:p.Arg4861Cys
NP_001036188.1:p.Arg4856Cys
LRG_766t1:c.14581C>T
LRG_766:g.151740C>T
LRG_766p1:p.Arg4861Cys
NC_000019.9:g.39071079C>T
NC_000019.9:g.39071079C>T
NM_000540.2:c.14581C>T
NP_000531.2:p.R4861C
P21817:p.Arg4861Cys
p.(Arg4861Cys)

Protein change:

R4856C

Links:

UniProtKB: P21817#VAR_045762; dbSNP: rs118192181

NCBI 1000 Genomes Browser:

rs118192181

Molecular consequence:

NM_000540.3:c.14581C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001042723.2:c.14566C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Mus musculus poly(rC) binding protein 4 (Pcbp4), mRNA
Mus musculus poly(rC) binding protein 4 (Pcbp4), mRNA
gi|359718936|ref|NM_021567.5|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000154439	Leiden Muscular Dystrophy (RYR1)	no classification provided	not provided	unknown	not provided	PubMed (3) [See all records that cite these PMIDs] 17226826, 17483490, 16621918
SCV000329691	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Nov 9, 2021)	germline	clinical testing	Citation Link,
SCV000510708	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 27, 2016)	de novo	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000852432	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 22, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001928785	Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001958401	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV003827271	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jun 26, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	de novo	not provided	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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Central core disease due to recessive mutations in RYR1 gene: is it more common than described?

Kossugue PM, Paim JF, Navarro MM, Silva HC, Pavanello RC, Gurgel-Giannetti J, Zatz M, Vainzof M.

Muscle Nerve. 2007 May;35(5):670-4.

PubMed [citation]

PMID:: 17226826

Molecular mechanisms and phenotypic variation in RYR1-related congenital myopathies.

Zhou H, Jungbluth H, Sewry CA, Feng L, Bertini E, Bushby K, Straub V, Roper H, Rose MR, Brockington M, Kinali M, Manzur A, Robb S, Appleton R, Messina S, D'Amico A, Quinlivan R, Swash M, Müller CR, Brown S, Treves S, Muntoni F.

Brain. 2007 Aug;130(Pt 8):2024-36. Epub 2007 May 4.

PubMed [citation]

PMID:: 17483490

See all PubMed Citations (4)

Details of each submission

From Leiden Muscular Dystrophy (RYR1), SCV000154439.1

#	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, SCV000329691.9

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

Description

Reported in multiple individuals with autosomal dominant central core disease with histological confirmation of central cores on muscle biopsy (Davis et al., 2003; Bharucja-Goebel et al, 2013); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 12565913, 23553484, 20301565, 26684984, 32403337, 33333461, 33184643, 33458582, 20681998)

#	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 Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics, SCV000510708.1

#	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	de novo	not provided	not provided	not provided	not provided		not provided	0.000111	not provided	not provided

From PreventionGenetics, part of Exact Sciences, SCV000852432.1

#	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 Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001928785.1

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

#	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 Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001958401.1

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

#	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, SCV003827271.2

#	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: Oct 26, 2024

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