NM_000540.3(RYR1):c.4978C>G (p.Arg1660Gly) AND RYR1-related disorder

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 27, 2021
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:: RCV000655573.6

Allele description [Variation Report for NM_000540.3(RYR1):c.4978C>G (p.Arg1660Gly)]

NM_000540.3(RYR1):c.4978C>G (p.Arg1660Gly)

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.4978C>G (p.Arg1660Gly)

HGVS:

NC_000019.10:g.38485633C>G
NG_008866.1:g.56934C>G
NM_000540.3:c.4978C>GMANE SELECT
NM_001042723.2:c.4978C>G
NP_000531.2:p.Arg1660Gly
NP_000531.2:p.Arg1660Gly
NP_001036188.1:p.Arg1660Gly
LRG_766t1:c.4978C>G
LRG_766:g.56934C>G
LRG_766p1:p.Arg1660Gly
NC_000019.9:g.38976273C>G
NM_000540.2:c.4978C>G

Protein change:

R1660G

Links:

dbSNP: rs1131691406

NCBI 1000 Genomes Browser:

rs1131691406

Molecular consequence:

NM_000540.3:c.4978C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001042723.2:c.4978C>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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Gene Links for GEO Profiles (Select 76525012) (2)
Gene
HUVECs infected with Staphylococcus aureus isolates from blood and anterior nare...
HUVECs infected with Staphylococcus aureus isolates from blood and anterior nares
Accession: GDS4030

GEO DataSets
Related DataSets for GEO Profiles (Select 76514186) (1)
GEO DataSets
Sphingomonas adhaesiva NBRC 15099, whole genome shotgun sequence
Sphingomonas adhaesiva NBRC 15099, whole genome shotgun sequence
gi|1054961259|ref|NZ_BCWT01000562.1

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000777504	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 27, 2021)	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

SCV000777504

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 27, 2021)

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, SCV000777504.3

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

Description

This sequence change replaces arginine with glycine at codon 1660 of the RYR1 protein (p.Arg1660Gly). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with RYR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 429482). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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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