NM_000540.3(RYR1):c.3257G>A (p.Arg1086His) AND RYR1-Related Disorders

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 12, 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:: RCV000693576.8

Allele description [Variation Report for NM_000540.3(RYR1):c.3257G>A (p.Arg1086His)]

NM_000540.3(RYR1):c.3257G>A (p.Arg1086His)

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.3257G>A (p.Arg1086His)

HGVS:

NC_000019.10:g.38467688G>A
NG_008866.1:g.38989G>A
NM_000540.3:c.3257G>AMANE SELECT
NM_001042723.2:c.3257G>A
NP_000531.2:p.Arg1086His
NP_000531.2:p.Arg1086His
NP_001036188.1:p.Arg1086His
LRG_766t1:c.3257G>A
LRG_766:g.38989G>A
LRG_766p1:p.Arg1086His
NC_000019.9:g.38958328G>A
NM_000540.2:c.3257G>A

Protein change:

R1086H

Links:

dbSNP: rs764009626

NCBI 1000 Genomes Browser:

rs764009626

Molecular consequence:

NM_000540.3:c.3257G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001042723.2:c.3257G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: RYR1-Related Disorders
Identifiers:: MedGen: CN239331

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000821449	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 12, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 3356401, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000821449

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 12, 2022)

germline

clinical testing

PubMed (2)
[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

Intrahepatic pressure measurement: not an accurate reflection of portal vein pressure.

Fenyves D, Pomier-Layrargues G, Willems B, Côté J.

Hepatology. 1988 Mar-Apr;8(2):211-6.

PubMed [citation]

PMID:: 3356401

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000821449.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1086 of the RYR1 protein (p.Arg1086His). This variant is present in population databases (rs764009626, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of autosomal dominant congenital myopathy and/or malignant hyperthermia (PMID: 3356401; Invitae). ClinVar contains an entry for this variant (Variation ID: 572240). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RYR1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Apr 20, 2024

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