NM_000540.3(RYR1):c.11697G>T (p.Gln3899His) AND RYR1-related disorder

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 29, 2016
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:: RCV000536226.7

Allele description [Variation Report for NM_000540.3(RYR1):c.11697G>T (p.Gln3899His)]

NM_000540.3(RYR1):c.11697G>T (p.Gln3899His)

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.11697G>T (p.Gln3899His)

HGVS:

NC_000019.10:g.38543354G>T
NG_008866.1:g.114655G>T
NM_000540.3:c.11697G>TMANE SELECT
NM_001042723.2:c.11682G>T
NP_000531.2:p.Gln3899His
NP_000531.2:p.Gln3899His
NP_001036188.1:p.Gln3894His
LRG_766t1:c.11697G>T
LRG_766:g.114655G>T
LRG_766p1:p.Gln3899His
NC_000019.9:g.39033994G>T
NM_000540.2:c.11697G>T

Protein change:

Q3894H

Links:

dbSNP: rs1555794184

NCBI 1000 Genomes Browser:

rs1555794184

Molecular consequence:

NM_000540.3:c.11697G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001042723.2:c.11682G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: RYR1-related disorder
Synonyms:: RYR1-Related Disorders; RYR1-related condition
Identifiers:: MedGen: CN239331

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COS12 Cos12p [Saccharomyces cerevisiae S288C]
COS12 Cos12p [Saccharomyces cerevisiae S288C]
Gene ID:852628

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000659774	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 29, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000659774

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 29, 2016)

germline

clinical testing

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

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

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000659774.4

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

Description

In summary, this variant is a novel missense change with uncertain impact on protein function. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a RYR1-related disease. This sequence change replaces glutamine with histidine at codon 3899 of the RYR1 protein (p.Gln3899His). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and histidine.

#	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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