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NM_000540.3(RYR1):c.7208G>A (p.Arg2403His) AND RYR1-related disorder

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 15, 2023
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:
RCV001300863.7

Allele description [Variation Report for NM_000540.3(RYR1):c.7208G>A (p.Arg2403His)]

NM_000540.3(RYR1):c.7208G>A (p.Arg2403His)

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.7208G>A (p.Arg2403His)
HGVS:
  • NC_000019.10:g.38499815G>A
  • NG_008866.1:g.71116G>A
  • NM_000540.2:c.7208G>A
  • NM_000540.3:c.7208G>AMANE SELECT
  • NM_001042723.2:c.7208G>A
  • NP_000531.2:p.Arg2403His
  • NP_001036188.1:p.Arg2403His
  • LRG_766t1:c.7208G>A
  • LRG_766:g.71116G>A
  • NC_000019.9:g.38990455G>A
Protein change:
R2403H
Links:
dbSNP: rs749136416
NCBI 1000 Genomes Browser:
rs749136416
Molecular consequence:
  • NM_000540.3:c.7208G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001042723.2:c.7208G>A - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001490013Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 15, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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, SCV001490013.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 2403 of the RYR1 protein (p.Arg2403His). This variant is present in population databases (rs749136416, gnomAD 0.04%). This missense change has been observed in individual(s) with clinical features of RYR1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 1004193). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 8, 2024