NM_000540.3(RYR1):c.5315G>C (p.Arg1772Thr) AND RYR1-related disorder

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 10, 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:: RCV001317221.7

Allele description [Variation Report for NM_000540.3(RYR1):c.5315G>C (p.Arg1772Thr)]

NM_000540.3(RYR1):c.5315G>C (p.Arg1772Thr)

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.5315G>C (p.Arg1772Thr)

HGVS:

NC_000019.10:g.38485970G>C
NG_008866.1:g.57271G>C
NM_000540.3:c.5315G>CMANE SELECT
NM_001042723.2:c.5315G>C
NP_000531.2:p.Arg1772Thr
NP_001036188.1:p.Arg1772Thr
LRG_766:g.57271G>C
NC_000019.9:g.38976610G>C

Protein change:

R1772T

Links:

dbSNP: rs1568484843

NCBI 1000 Genomes Browser:

rs1568484843

Molecular consequence:

NM_000540.3:c.5315G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001042723.2:c.5315G>C - 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
SCV001507872	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 10, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23553484, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001507872

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 10, 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

Severe congenital RYR1-associated myopathy: the expanding clinicopathologic and genetic spectrum.

Bharucha-Goebel DX, Santi M, Medne L, Zukosky K, Dastgir J, Shieh PB, Winder T, Tennekoon G, Finkel RS, Dowling JJ, Monnier N, Bönnemann CG.

Neurology. 2013 Apr 23;80(17):1584-9. doi: 10.1212/WNL.0b013e3182900380. Epub 2013 Apr 3. Erratum in: Neurology. 2013 May 28;80(22):2081. Zukosky, Kristin [corrected to Zukosky, Kristen].

PubMed [citation]

PMID:: 23553484
PMCID:: PMC3662324

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, SCV001507872.4

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

Description

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. The observation of one or more missense substitutions at this codon (p.Arg1772Gly) in affected individuals suggests that this may be a clinically significant residue (PMID: 23553484). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with RYR1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with threonine at codon 1772 of the RYR1 protein (p.Arg1772Thr). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and threonine.

#	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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