NM_000540.3(RYR1):c.8290G>A (p.Glu2764Lys) AND not provided

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Mar 11, 2024
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:: RCV000119743.3

Allele description [Variation Report for NM_000540.3(RYR1):c.8290G>A (p.Glu2764Lys)]

NM_000540.3(RYR1):c.8290G>A (p.Glu2764Lys)

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.8290G>A (p.Glu2764Lys)

Other names:

NM_000540.3(RYR1):c.8290G>A

HGVS:

NC_000019.10:g.38505061G>A
NG_008866.1:g.76362G>A
NM_000540.3:c.8290G>AMANE SELECT
NM_001042723.2:c.8290G>A
NP_000531.2:p.Glu2764Lys
NP_000531.2:p.Glu2764Lys
NP_001036188.1:p.Glu2764Lys
LRG_766t1:c.8290G>A
LRG_766:g.76362G>A
LRG_766p1:p.Glu2764Lys
NC_000019.9:g.38995701G>A
NM_000540.2:c.8290G>A
p.(Glu2764Lys)

Protein change:

E2764K

Links:

dbSNP: rs193922829

NCBI 1000 Genomes Browser:

rs193922829

Molecular consequence:

NM_000540.3:c.8290G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001042723.2:c.8290G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000154650	Leiden Muscular Dystrophy (RYR1)	no classification provided	not provided	unknown	not provided	PubMed (1) [See all records that cite this PMID]
SCV004025572	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Mar 11, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000154650

Leiden Muscular Dystrophy (RYR1)

no classification provided

not provided

unknown

not provided

PubMed (1)
[See all records that cite this PMID]

SCV004025572

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Mar 11, 2024)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	not provided	not provided	not provided	not provided	1	not provided	literature only

Citations

PubMed

Frequency and localization of mutations in the 106 exons of the RYR1 gene in 50 individuals with malignant hyperthermia.

Galli L, Orrico A, Lorenzini S, Censini S, Falciani M, Covacci A, Tegazzin V, Sorrentino V.

Hum Mutat. 2006 Aug;27(8):830.

PubMed [citation]

PMID:: 16835904

Details of each submission

From Leiden Muscular Dystrophy (RYR1), SCV000154650.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	not provided	1	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV004025572.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Reported previously as a heterozygous variant in an individual with repeated episodes of generalized normokalemic paralysis (PMID: 31068157); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22705209, 35677449, 31068157, 16835904, 12668474)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 18, 2024

ClinVar

Relating variation to medicine