NM_000540.3(RYR1):c.7039GAG[1] (p.Glu2348del) AND RYR1-related disorder

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 27, 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:: RCV001384027.13

Allele description [Variation Report for NM_000540.3(RYR1):c.7039GAG[1] (p.Glu2348del)]

NM_000540.3(RYR1):c.7039GAG[1] (p.Glu2348del)

Gene:

RYR1:ryanodine receptor 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

19q13.2

Genomic location:

Preferred name:

NM_000540.3(RYR1):c.7039GAG[1] (p.Glu2348del)

Other names:

E2347del; NM_001042723.2(RYR1):c.7039_7041GAG[1]; p.Glu2348del

HGVS:

NC_000019.10:g.38499646GAG[1]
NC_000019.10:g.38499646_38499648del
NG_008866.1:g.70947GAG[1]
NM_000540.3:c.7039GAG[1]MANE SELECT
NM_001042723.2:c.7039GAG[1]
NP_000531.2:p.Glu2348del
NP_001036188.1:p.Glu2348del
LRG_766:g.70947GAG[1]
NC_000019.10:g.38499646_38499648GAG[1]
NC_000019.10:g.38499646_38499648del
NC_000019.9:g.38990285_38990287del
NC_000019.9:g.38990286GAG[1]
NM_000540.2:c.7042_7044delGAG
p.(Glu2348del)

Protein change:

E2348del; GLU2347DEL

Links:

OMIM: 180901.0017; OMIM: 180901.0041; dbSNP: rs121918596

NCBI 1000 Genomes Browser:

rs121918596

Molecular consequence:

NM_000540.3:c.7039GAG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001042723.2:c.7039GAG[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

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
SCV001583390	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 27, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 28687594, 11389482, 27857962, 25476234, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001583390

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 27, 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

Reduced threshold for store overload-induced Ca(2+) release is a common defect of RyR1 mutations associated with malignant hyperthermia and central core disease.

Chen W, Koop A, Liu Y, Guo W, Wei J, Wang R, MacLennan DH, Dirksen RT, Chen SRW.

Biochem J. 2017 Aug 7;474(16):2749-2761. doi: 10.1042/BCJ20170282.

PubMed [citation]

PMID:: 28687594
PMCID:: PMC5803747

Single-amino-acid deletion in the RYR1 gene, associated with malignant hyperthermia susceptibility and unusual contraction phenotype.

Sambuughin N, McWilliams S, de Bantel A, Sivakumar K, Nelson TE.

Am J Hum Genet. 2001 Jul;69(1):204-8. Epub 2001 May 29.

PubMed [citation]

PMID:: 11389482
PMCID:: PMC1226035

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001583390.4

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

Description

This variant, c.7042_7044del, results in the deletion of 1 amino acid(s) of the RYR1 protein (p.Glu2348del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs758046764, gnomAD 0.0009%). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this variant affects RYR1 function (PMID: 27857962, 28687594). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 133180). This variant is also known as E2347del. This variant has been observed in individual(s) with autosomal dominant malignant hyperthermia susceptibility (PMID: 11389482, 27857962). It has also been observed to segregate with disease in related individuals. This variant has been reported in individual(s) with autosomal recessive congenital fiber type disproportion (PMID: 25476234); however, the role of the variant in this condition is currently unclear.

#	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: Oct 13, 2024

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