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NM_000540.3(RYR1):c.12759del (p.Glu4254fs) AND RYR1-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 24, 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:
RCV002871589.3

Allele description [Variation Report for NM_000540.3(RYR1):c.12759del (p.Glu4254fs)]

NM_000540.3(RYR1):c.12759del (p.Glu4254fs)

Gene:
RYR1:ryanodine receptor 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
19q13.2
Genomic location:
Preferred name:
NM_000540.3(RYR1):c.12759del (p.Glu4254fs)
HGVS:
  • NC_000019.10:g.38565093del
  • NG_008866.1:g.136394del
  • NM_000540.3:c.12759delMANE SELECT
  • NM_001042723.2:c.12744del
  • NP_000531.2:p.Glu4254Argfs
  • NP_000531.2:p.Glu4254fs
  • NP_001036188.1:p.Glu4249fs
  • LRG_766t1:c.12759del
  • LRG_766:g.136394del
  • LRG_766p1:p.Glu4254Argfs
  • NC_000019.9:g.39055731del
  • NC_000019.9:g.39055733del
  • NM_000540.2:c.12759delC
Protein change:
E4249fs
Molecular consequence:
  • NM_000540.3:c.12759del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001042723.2:c.12744del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003232230Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Aug 24, 2022) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

RYR1 mutations are a common cause of congenital myopathies with central nuclei.

Wilmshurst JM, Lillis S, Zhou H, Pillay K, Henderson H, Kress W, Müller CR, Ndondo A, Cloke V, Cullup T, Bertini E, Boennemann C, Straub V, Quinlivan R, Dowling JJ, Al-Sarraj S, Treves S, Abbs S, Manzur AY, Sewry CA, Muntoni F, Jungbluth H.

Ann Neurol. 2010 Nov;68(5):717-26. doi: 10.1002/ana.22119.

PubMed [citation]
PMID:
20839240
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003232230.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This variant has not been reported in the literature in individuals affected with RYR1-related conditions. For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu4254Argfs*87) 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: 20583297, 20839240, 23919265, 28818389).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024