NM_000540.3(RYR1):c.14833C>T (p.Arg4945Ter) AND RYR1-related disorder

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 19, 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:: RCV000541517.7

Allele description [Variation Report for NM_000540.3(RYR1):c.14833C>T (p.Arg4945Ter)]

NM_000540.3(RYR1):c.14833C>T (p.Arg4945Ter)

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.14833C>T (p.Arg4945Ter)

HGVS:

NC_000019.10:g.38585967C>T
NG_008866.1:g.157268C>T
NM_000540.3:c.14833C>TMANE SELECT
NM_001042723.2:c.14818C>T
NP_000531.2:p.Arg4945Ter
NP_000531.2:p.Arg4945Ter
NP_001036188.1:p.Arg4940Ter
LRG_766t1:c.14833C>T
LRG_766:g.157268C>T
LRG_766p1:p.Arg4945Ter
NC_000019.9:g.39076607C>T
NM_000540.2:c.14833C>T

Protein change:

R4940*

Links:

dbSNP: rs1432807966

NCBI 1000 Genomes Browser:

rs1432807966

Molecular consequence:

NM_000540.3:c.14833C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001042723.2:c.14818C>T - 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
SCV000659860	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 19, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 23919265, 25960145, 28818389, 30611313, 29172004, 24433488, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000659860

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 19, 2023)

germline

clinical testing

PubMed (7)
[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

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

Snoeck M, van Engelen BG, Küsters B, Lammens M, Meijer R, Molenaar JP, Raaphorst J, Verschuuren-Bemelmans CC, Straathof CS, Sie LT, de Coo IF, van der Pol WL, de Visser M, Scheffer H, Treves S, Jungbluth H, Voermans NC, Kamsteeg EJ.

Eur J Neurol. 2015 Jul;22(7):1094-112. doi: 10.1111/ene.12713. Epub 2015 May 11.

PubMed [citation]

PMID:: 25960145

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000659860.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change creates a premature translational stop signal (p.Arg4945*) 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). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with autosomal recessive congenital myopathy (PMID: 29172004). This variant has been reported in individual(s) with autosomal dominant malignant hyperthermia susceptibility (PMID: 24433488); however, the role of the variant in this condition is currently unclear. ClinVar contains an entry for this variant (Variation ID: 478201). For these reasons, this variant has been classified as Pathogenic.

#	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 24, 2024

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