U.S. flag

An official website of the United States government

NM_000540.3(RYR1):c.14423T>A (p.Phe4808Tyr) AND Central core myopathy

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Sep 1, 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:
RCV002283577.1

Allele description [Variation Report for NM_000540.3(RYR1):c.14423T>A (p.Phe4808Tyr)]

NM_000540.3(RYR1):c.14423T>A (p.Phe4808Tyr)

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.14423T>A (p.Phe4808Tyr)
HGVS:
  • NC_000019.10:g.38580040T>A
  • NG_008866.1:g.151341T>A
  • NM_000540.3:c.14423T>AMANE SELECT
  • NM_001042723.2:c.14408T>A
  • NP_000531.2:p.Phe4808Tyr
  • NP_001036188.1:p.Phe4803Tyr
  • LRG_766:g.151341T>A
  • NC_000019.9:g.39070680T>A
Protein change:
F4803Y
Links:
dbSNP: rs1274780855
NCBI 1000 Genomes Browser:
rs1274780855
Molecular consequence:
  • NM_000540.3:c.14423T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042723.2:c.14408T>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Central core myopathy (CMYO1A)
Synonyms:
Central core disease; Central core disease of muscle; Muscle core disease; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007294; MedGen: C0751951; Orphanet: 597; OMIM: 117000

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
SCV0025731993billion
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Sep 1, 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

Congenital myopathies--clinical features and frequency of individual subtypes diagnosed over a 5-year period in the United Kingdom.

Maggi L, Scoto M, Cirak S, Robb SA, Klein A, Lillis S, Cullup T, Feng L, Manzur AY, Sewry CA, Abbs S, Jungbluth H, Muntoni F.

Neuromuscul Disord. 2013 Mar;23(3):195-205. doi: 10.1016/j.nmd.2013.01.004. Epub 2013 Feb 8.

PubMed [citation]
PMID:
23394784

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, SCV002573199.1

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

Description

The variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.94; 3Cnet: 0.86). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with RYR1-related disorder (ClinVar ID: VCV001498872 / PMID: 23394784). Different missense changes at the same codon (p.Phe4808Asn, p.Phe4808Leu) have been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000478199 , VCV001213684). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Sep 29, 2024