NM_001035.3(RYR2):c.848C>T (p.Ala283Val) AND Cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 11, 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:: RCV001524133.11

Allele description [Variation Report for NM_001035.3(RYR2):c.848C>T (p.Ala283Val)]

NM_001035.3(RYR2):c.848C>T (p.Ala283Val)

Gene:

RYR2:ryanodine receptor 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q43

Genomic location:

Preferred name:

NM_001035.3(RYR2):c.848C>T (p.Ala283Val)

HGVS:

NC_000001.11:g.237417123C>T
NG_008799.3:g.379940C>T
NM_001035.3:c.848C>TMANE SELECT
NP_001026.2:p.Ala283Val
LRG_402t1:c.848C>T
LRG_402:g.379940C>T
LRG_402p1:p.Ala283Val
NC_000001.10:g.237580423C>T
NM_001035.2:c.848C>T

Protein change:

A283V

Links:

dbSNP: rs1163526442

NCBI 1000 Genomes Browser:

rs1163526442

Molecular consequence:

NM_001035.3:c.848C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiomyopathy (CMYO)
Synonyms:: Cardiomyopathies
Identifiers:: MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

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V-set and transmembrane domain-containing protein 1 isoform 1 precursor [Homo sa...
V-set and transmembrane domain-containing protein 1 isoform 1 precursor [Homo sapiens]
gi|145580634|ref|NP_940883.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001733902	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 11, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28404607, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001733902

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 11, 2023)

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

Interpreting Incidentally Identified Variants in Genes Associated With Catecholaminergic Polymorphic Ventricular Tachycardia in a Large Cohort of Clinical Whole-Exome Genetic Test Referrals.

Landstrom AP, Dailey-Schwartz AL, Rosenfeld JA, Yang Y, McLean MJ, Miyake CY, Valdes SO, Fan Y, Allen HD, Penny DJ, Kim JJ.

Circ Arrhythm Electrophysiol. 2017 Apr;10(4). doi:pii: e004742. 10.1161/CIRCEP.116.004742.

PubMed [citation]

PMID:: 28404607
PMCID:: PMC5391872

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001733902.2

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

Description

This missense variant replaces alanine with valine at codon 283 of the RYR2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual from a cohort of clinical whole-exome genetic test referrals (PMID: 28404607). This variant has been identified in 1/248868 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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: Oct 26, 2024

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