NM_000540.3(RYR1):c.14110C>T (p.Arg4704Ter) AND RYR1-related disorder

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 3, 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:: RCV001053096.12

Allele description [Variation Report for NM_000540.3(RYR1):c.14110C>T (p.Arg4704Ter)]

NM_000540.3(RYR1):c.14110C>T (p.Arg4704Ter)

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.14110C>T (p.Arg4704Ter)

HGVS:

NC_000019.10:g.38573288C>T
NG_008866.1:g.144589C>T
NM_000540.3:c.14110C>TMANE SELECT
NM_001042723.2:c.14095C>T
NP_000531.2:p.Arg4704Ter
NP_001036188.1:p.Arg4699Ter
LRG_766t1:c.14110C>T
LRG_766:g.144589C>T
NC_000019.9:g.39063928C>T
NM_000540.2:c.14110C>T

Protein change:

R4699*

Links:

dbSNP: rs1568595930

NCBI 1000 Genomes Browser:

rs1568595930

Molecular consequence:

NM_000540.3:c.14110C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001042723.2:c.14095C>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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aquaporin-4 isoform M23 [Homo sapiens]
aquaporin-4 isoform M23 [Homo sapiens]
gi|4755125|ref|NP_004019.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001217338	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 3, 2022)	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

SCV001217338

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 3, 2022)

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 Invitae, SCV001217338.5

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 849189). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg4704*) 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).

#	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: Aug 4, 2024

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