U.S. flag

An official website of the United States government

NM_000540.3(RYR1):c.14833C>T (p.Arg4945Ter) AND Congenital multicore myopathy with external ophthalmoplegia

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 22, 2022
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:
RCV002250657.1

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]
Observations:
1

Condition(s)

Name:
Congenital multicore myopathy with external ophthalmoplegia (CMYO1B)
Synonyms:
MULTICORE MYOPATHY; Minicore myopathy with external ophthalmoplegia; Multicore myopathy with external ophthalmoplegia; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009712; MedGen: C1850674; Orphanet: 598; OMIM: 255320; Human Phenotype Ontology: HP:0003789

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV0025217193billion
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(May 22, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot provided1not providedclinical testing

Citations

PubMed

Early-Onset Myopathies: Clinical Findings, Prevalence of Subgroups and Diagnostic Approach in a Single Neuromuscular Referral Center in Germany.

Vill K, Blaschek A, Gläser D, Kuhn M, Haack T, Alhaddad B, Wagner M, Kovacs-Nagy R, Tacke M, Gerstl L, Schroeder AS, Borggraefe I, Mueller C, Schlotter-Weigel B, Schoser B, Walter MC, Müller-Felber W.

J Neuromuscul Dis. 2017;4(4):315-325. doi: 10.3233/JND-170231.

PubMed [citation]
PMID:
29172004

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From 3billion, SCV002521719.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.003%). Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000478201 / PMID: 29172004). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyes1not providednot provided1not providednot providednot provided

Last Updated: Nov 24, 2024