NM_001035.3(RYR2):c.506G>A (p.Arg169Gln) AND Catecholaminergic polymorphic ventricular tachycardia

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 27, 2013
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:: RCV000036762.8

Allele description [Variation Report for NM_001035.3(RYR2):c.506G>A (p.Arg169Gln)]

NM_001035.3(RYR2):c.506G>A (p.Arg169Gln)

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.506G>A (p.Arg169Gln)

Other names:

p.R169Q:CGA>CAA

HGVS:

NC_000001.11:g.237377365G>A
NG_008799.3:g.340182G>A
NM_001035.3:c.506G>AMANE SELECT
NP_001026.2:p.Arg169Gln
LRG_402t1:c.506G>A
LRG_402:g.340182G>A
LRG_402p1:p.Arg169Gln
NC_000001.10:g.237540665G>A
NG_008799.2:g.339964G>A
NM_001035.2:c.506G>A
c.506G>A

Protein change:

R169Q

Links:

dbSNP: rs397516539

NCBI 1000 Genomes Browser:

rs397516539

Molecular consequence:

NM_001035.3:c.506G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Catecholaminergic polymorphic ventricular tachycardia (CVPT)
Synonyms:: Familial polymorphic ventricular tachycardia; Catecholamine-induced polymorphic ventricular tachycardia; Polymorphic catecholergic ventricular tachycardia
Identifiers:: MONDO: MONDO:0017990; MedGen: C5574922; Orphanet: 3286; OMIM: PS604772

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000060417	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely pathogenic (Aug 27, 2013)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 16517285, 19926015, 20961976, 19541610, 19913485, 23595086, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000060417

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely pathogenic
(Aug 27, 2013)

germline

clinical testing

PubMed (7)
[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	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

A novel mutation (Arg169Gln) of the cardiac ryanodine receptor gene causing exercise-induced bidirectional ventricular tachycardia.

Hsueh CH, Weng YC, Chen CY, Lin TK, Lin YH, Lai LP, Lin JL.

Int J Cardiol. 2006 Apr 4;108(2):276-8.

PubMed [citation]

PMID:: 16517285

The RYR2-encoded ryanodine receptor/calcium release channel in patients diagnosed previously with either catecholaminergic polymorphic ventricular tachycardia or genotype negative, exercise-induced long QT syndrome: a comprehensive open reading frame mutational analysis.

Medeiros-Domingo A, Bhuiyan ZA, Tester DJ, Hofman N, Bikker H, van Tintelen JP, Mannens MM, Wilde AA, Ackerman MJ.

J Am Coll Cardiol. 2009 Nov 24;54(22):2065-74. doi: 10.1016/j.jacc.2009.08.022.

PubMed [citation]

PMID:: 19926015
PMCID:: PMC2880864

See all PubMed Citations (7)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000060417.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (7)

Description

The Arg169Gln variant in RYR2 has been reported in 3 Asian individuals with CPVT , was reported to occur de novo in one of these individuals, and was absent from 200 control chromosomes (Hsueh 2006, Ge 2012, Kawamura 2013). This variant has been identified by our laboratory in 1 Caucasian individual with LVNC and bidire ctional VT, and was not identified in large population studies. Arginine (Arg) a t position 169 is highly conserved in mammals and across evolutionarily distant species and computational analyses (AlignGVGD, PolyPhen2, and SIFT) suggest that the Arg169Gln variant may impact the protein, which raises the possibility that a change at this position might not be tolerated. Additionally, this variant is located in a conserved domain of the RYR2 protein that may be critical for prot ein interactions and where other variants are clustered (Amador 2009, Lobo 2009) . In summary, this variant is likely to be pathogenic, though additional studies are required to fully establish its clinical significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		1	not provided	1	not provided

Last Updated: May 1, 2024

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