NM_000540.3(RYR1):c.7850C>A (p.Ser2617Ter) AND RYR1-related disorder

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 3, 2021
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:: RCV001947997.4

Allele description [Variation Report for NM_000540.3(RYR1):c.7850C>A (p.Ser2617Ter)]

NM_000540.3(RYR1):c.7850C>A (p.Ser2617Ter)

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.7850C>A (p.Ser2617Ter)

HGVS:

NC_000019.10:g.38502894C>A
NG_008866.1:g.74195C>A
NM_000540.3:c.7850C>AMANE SELECT
NM_001042723.2:c.7850C>A
NP_000531.2:p.Ser2617Ter
NP_001036188.1:p.Ser2617Ter
LRG_766:g.74195C>A
NC_000019.9:g.38993534C>A

Protein change:

S2617*

Links:

dbSNP: rs780836747

NCBI 1000 Genomes Browser:

rs780836747

Molecular consequence:

NM_000540.3:c.7850C>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001042723.2:c.7850C>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
SCV002194952	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 3, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 20583297, 20839240, 23919265, 28818389, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002194952

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 3, 2021)

germline

clinical testing

PubMed (5)
[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

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, SCV002194952.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change creates a premature translational stop signal (p.Ser2617*) 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). This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with RYR1-related conditions.

#	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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