NM_001042723.2(RYR1):c.1739_1742dup (p.His581fs) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 10, 2016
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:: RCV000119584.1

Allele description

NM_001042723.2(RYR1):c.1739_1742dup (p.His581fs)

Gene:

RYR1:ryanodine receptor 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

19q13.2

Genomic location:

Preferred name:

NM_001042723.2(RYR1):c.1739_1742dup (p.His581fs)

HGVS:

NC_000019.10:g.38455699_38455702dup
NG_008866.1:g.27000_27003dup
NM_001042723.2:c.1739_1742dup
NP_001036188.1:p.His581fs
LRG_766t1:c.1739_1742dup
LRG_766:g.27000_27003dup
LRG_766p1:p.His581fs
NC_000019.9:g.38946339_38946342dup
NM_000540.2:c.1739_1742dupATCA
p.(His581Glnfs*30)
r.(?)

Protein change:

H581fs

Links:

OMIM: 180901.0032; dbSNP: rs193922771

NCBI 1000 Genomes Browser:

rs193922771

Molecular consequence:

NM_001042723.2:c.1739_1742dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000154491	Leiden Muscular Dystrophy (RYR1)	no classification provided	not provided	unknown	not provided	PubMed (1) [See all records that cite this PMID]
SCV000568771	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Nov 10, 2016)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000154491

Leiden Muscular Dystrophy (RYR1)

no classification provided

not provided

unknown

not provided

PubMed (1)
[See all records that cite this PMID]

SCV000568771

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Nov 10, 2016)

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

Null mutations causing depletion of the type 1 ryanodine receptor (RYR1) are commonly associated with recessive structural congenital myopathies with cores.

Monnier N, Marty I, Faure J, Castiglioni C, Desnuelle C, Sacconi S, Estournet B, Ferreiro A, Romero N, Laquerriere A, Lazaro L, Martin JJ, Morava E, Rossi A, Van der Kooi A, de Visser M, Verschuuren C, Lunardi J.

Hum Mutat. 2008 May;29(5):670-8. doi: 10.1002/humu.20696.

PubMed [citation]

PMID:: 18253926

Details of each submission

From Leiden Muscular Dystrophy (RYR1), SCV000154491.1

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

#	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, SCV000568771.4

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

Description

The c.1739_1742dupATCA variant in the RYR1 gene has been reported previously in association with autosomal recessive congenital myopathy, in an affected individual who was compound heterozygous for the c.1739_1742dupATCA variant and a missense variant in the RYR1 gene (Monnier et al., 2008). The c.1739_1742dupATCA variant causes a frameshift starting with codon Histidine 581, changes this amino acid to a Glutamine residue, and creates a premature Stop codon at position 30 of the new reading frame, denoted p.His581GlnfsX30. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1739_1742dupATCA variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1739_1742dupATCA as a pathogenic variant.

#	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: Apr 13, 2021

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