NM_000540.3(RYR1):c.85A>G (p.Lys29Glu) AND RYR1-related disorder

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 24, 2018
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:: RCV001315872.7

Allele description [Variation Report for NM_000540.3(RYR1):c.85A>G (p.Lys29Glu)]

NM_000540.3(RYR1):c.85A>G (p.Lys29Glu)

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.85A>G (p.Lys29Glu)

HGVS:

NC_000019.10:g.38440784A>G
NG_008866.1:g.12085A>G
NM_000540.3:c.85A>GMANE SELECT
NM_001042723.2:c.85A>G
NP_000531.2:p.Lys29Glu
NP_001036188.1:p.Lys29Glu
LRG_766:g.12085A>G
NC_000019.9:g.38931424A>G

Protein change:

K29E

Links:

dbSNP: rs1240489600

NCBI 1000 Genomes Browser:

rs1240489600

Molecular consequence:

NM_000540.3:c.85A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001042723.2:c.85A>G - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001506466	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 24, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16084090, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001506466

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 24, 2018)

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

Ryanodine receptor 1 mutations, dysregulation of calcium homeostasis and neuromuscular disorders.

Treves S, Anderson AA, Ducreux S, Divet A, Bleunven C, Grasso C, Paesante S, Zorzato F.

Neuromuscul Disord. 2005 Oct;15(9-10):577-87. Review.

PubMed [citation]

PMID:: 16084090

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, SCV001506466.4

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

Description

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: "Possibly Damaging"; Align-GVGD: "Class C0"). This sequence change replaces lysine with glutamic acid at codon 29 of the RYR1 protein (p.Lys29Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RYR1-related disease. This missense change is located in a region of the RYR1 protein where a significant number of previously reported RYR1 missense mutations are found (PMID: 16084090). These observations suggest that a previously unreported missense substitution within this region may affect protein function, but experiments have not been done to test this possibility. 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: Sep 29, 2024

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