NM_001035.3(RYR2):c.995G>A (p.Arg332Gln) AND Catecholaminergic polymorphic ventricular tachycardia 1

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 31, 2020
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:: RCV002547460.9

Allele description

NM_001035.3(RYR2):c.995G>A (p.Arg332Gln)

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.995G>A (p.Arg332Gln)

HGVS:

NC_000001.11:g.237423238G>A
NG_008799.3:g.386055G>A
NM_001035.3:c.995G>AMANE SELECT
NP_001026.2:p.Arg332Gln
LRG_402t1:c.995G>A
LRG_402:g.386055G>A
LRG_402p1:p.Arg332Gln
NC_000001.10:g.237586538G>A

Protein change:

R332Q

Links:

dbSNP: rs1558793119

NCBI 1000 Genomes Browser:

rs1558793119

Molecular consequence:

NM_001035.3:c.995G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Catecholaminergic polymorphic ventricular tachycardia 1
Synonyms:: VENTRICULAR TACHYCARDIA, CATECHOLAMINERGIC POLYMORPHIC, 1, WITH OR WITHOUT ATRIAL DYSFUNCTION AND/OR DILATED CARDIOMYOPATHY; Stress-induced polymorphic ventricular tachycardia; VENTRICULAR TACHYCARDIA, STRESS-INDUCED POLYMORPHIC 1
Identifiers:: MONDO: MONDO:0011484; MedGen: C1631597; Orphanet: 3286; OMIM: 604772

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001541565	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 31, 2020)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28449774, 31112425, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001541565

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 31, 2020)

germline

clinical testing

PubMed (3)
[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

Utility of Post-Mortem Genetic Testing in Cases of Sudden Arrhythmic Death Syndrome.

Lahrouchi N, Raju H, Lodder EM, Papatheodorou E, Ware JS, Papadakis M, Tadros R, Cole D, Skinner JR, Crawford J, Love DR, Pua CJ, Soh BY, Bhalshankar JD, Govind R, Tfelt-Hansen J, Winkel BG, van der Werf C, Wijeyeratne YD, Mellor G, Till J, Cohen MC, et al.

J Am Coll Cardiol. 2017 May 2;69(17):2134-2145. doi: 10.1016/j.jacc.2017.02.046.

PubMed [citation]

PMID:: 28449774
PMCID:: PMC5405216

Assessment and Validation of a Phenotype-Enhanced Variant Classification Framework to Promote or Demote RYR2 Missense Variants of Uncertain Significance.

Giudicessi JR, Lieve KVV, Rohatgi RK, Koca F, Tester DJ, van der Werf C, Martijn Bos J, Wilde AAM, Ackerman MJ.

Circ Genom Precis Med. 2019 May;12(5):e002510. doi: 10.1161/CIRCGEN.119.002510.

PubMed [citation]

PMID:: 31112425

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001541565.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant has been reported in individual(s) with sudden arrhythmic death syndrome or suspected catecholaminergic polymorphic ventricular tachycardia (PMID: 28449774, 31112425). This sequence change replaces arginine with glutamine at codon 332 of the RYR2 protein (p.Arg332Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 16, 2024

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