NM_000540.3(RYR1):c.9851G>A (p.Trp3284Ter) AND RYR1-related disorder

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 16, 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:: RCV003591879.2

Allele description [Variation Report for NM_000540.3(RYR1):c.9851G>A (p.Trp3284Ter)]

NM_000540.3(RYR1):c.9851G>A (p.Trp3284Ter)

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.9851G>A (p.Trp3284Ter)

HGVS:

NC_000019.10:g.38517524G>A
NG_008866.1:g.88825G>A
NM_000540.3:c.9851G>AMANE SELECT
NM_001042723.2:c.9851G>A
NP_000531.2:p.Trp3284Ter
NP_001036188.1:p.Trp3284Ter
LRG_766:g.88825G>A
NC_000019.9:g.39008164G>A

Protein change:

W3284*

Links:

dbSNP: rs2145682223

NCBI 1000 Genomes Browser:

rs2145682223

Molecular consequence:

NM_000540.3:c.9851G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001042723.2:c.9851G>A - 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
SCV004297340	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 16, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 26932181, 23919265, 25960145, 28818389, 30611313, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004297340

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 16, 2023)

germline

clinical testing

PubMed (6)
[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

Lethal multiple pterygium syndrome, the extreme end of the RYR1 spectrum.

Kariminejad A, Ghaderi-Sohi S, Hossein-Nejad Nedai H, Varasteh V, Moslemi AR, Tajsharghi H.

BMC Musculoskelet Disord. 2016 Mar 1;17:109. doi: 10.1186/s12891-016-0947-5.

PubMed [citation]

PMID:: 26932181
PMCID:: PMC4774121

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 (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004297340.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1180626). This premature translational stop signal has been observed in individual(s) with clinical features of autosomal recessive RYR1-related conditions (PMID: 26932181). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp3284*) in the RYR1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RYR1 are known to be pathogenic (PMID: 23919265, 25960145, 28818389, 30611313).

#	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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