NM_000540.3(RYR1):c.14579_14580delinsAA (p.Phe4860Ter) AND RYR1-related disorder

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 15, 2017
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:: RCV000655506.4

Allele description [Variation Report for NM_000540.3(RYR1):c.14579_14580delinsAA (p.Phe4860Ter)]

NM_000540.3(RYR1):c.14579_14580delinsAA (p.Phe4860Ter)

Gene:

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

Variant type:

Indel

Cytogenetic location:

19q13.2

Genomic location:

Preferred name:

NM_000540.3(RYR1):c.14579_14580delinsAA (p.Phe4860Ter)

HGVS:

NC_000019.10:g.38580437_38580438delinsAA
NG_008866.1:g.151738_151739delinsAA
NM_000540.3:c.14579_14580delinsAAMANE SELECT
NM_001042723.2:c.14564_14565delinsAA
NP_000531.2:p.Phe4860Ter
NP_001036188.1:p.Phe4855Ter
LRG_766:g.151738_151739delinsAA
NC_000019.9:g.39071077_39071078delinsAA

Protein change:

F4855*

Links:

dbSNP: rs1555803960

NCBI 1000 Genomes Browser:

rs1555803960

Molecular consequence:

NM_000540.3:c.14579_14580delinsAA - nonsense - [Sequence Ontology: SO:0001587]
NM_001042723.2:c.14564_14565delinsAA - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: RYR1-related disorder
Synonyms:: RYR1-Related Disorders; RYR1-related condition
Identifiers:: MedGen: CN239331

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000777437	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 15, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 20583297, 23919265, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000777437

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 15, 2017)

germline

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion.

Clarke NF, Waddell LB, Cooper ST, Perry M, Smith RL, Kornberg AJ, Muntoni F, Lillis S, Straub V, Bushby K, Guglieri M, King MD, Farrell MA, Marty I, Lunardi J, Monnier N, North KN.

Hum Mutat. 2010 Jul;31(7):E1544-50. doi: 10.1002/humu.21278.

PubMed [citation]

PMID:: 20583297

Genotype-phenotype correlations in recessive RYR1-related myopathies.

Amburgey K, Bailey A, Hwang JH, Tarnopolsky MA, Bonnemann CG, Medne L, Mathews KD, Collins J, Daube JR, Wellman GP, Callaghan B, Clarke NF, Dowling JJ.

Orphanet J Rare Dis. 2013 Aug 6;8:117. doi: 10.1186/1750-1172-8-117.

PubMed [citation]

PMID:: 23919265
PMCID:: PMC3751094

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000777437.3

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

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in RYR1 are known to be pathogenic (PMID: 20583297, 23919265). This variant has not been reported in the literature in individuals with RYR1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe4860Tyr) in the RYR1 gene. It is expected to result in an absent or disrupted protein product.

#	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: Sep 29, 2024

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