NM_004572.3(PKP2):c.235C>T (p.Arg79Ter) AND Arrhythmogenic right ventricular cardiomyopathy, type 9

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

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 8, 2016
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:: RCV000007146.4

Allele description

NM_004572.3(PKP2):c.235C>T (p.Arg79Ter)

Gene:

PKP2:plakophilin 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12p11.21

Genomic location:

Preferred name:

NM_004572.3(PKP2):c.235C>T (p.Arg79Ter)

Other names:

p.R79*:CGA>TGA

HGVS:

NC_000012.12:g.32879021G>A
NG_009000.1:g.22826C>T
NM_004572.3:c.235C>T
NP_004563.2:p.Arg79Ter
LRG_398t1:c.235C>T
LRG_398:g.22826C>T
LRG_398p1:p.Arg79Ter
NC_000012.11:g.33031955G>A
c.235C>T
p.Arg79X

Protein change:

R79*; ARG79TER

Links:

OMIM: 602861.0001; dbSNP: rs121434420

NCBI 1000 Genomes Browser:

rs121434420

Molecular consequence:

NM_004572.3:c.235C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Arrhythmogenic right ventricular cardiomyopathy, type 9 (ARVD9)
Synonyms:: ARRHYTHMOGENIC RIGHT VENTRICULAR DYSPLASIA, FAMILIAL, 9; Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy 9
Identifiers:: MedGen: C1836906; OMIM: 609040

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000027342	OMIM	no assertion criteria provided	Pathogenic (Nov 1, 2004)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000288604	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 8, 2016)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000027342

OMIM

no assertion criteria provided

Pathogenic
(Nov 1, 2004)

germline

literature only

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

SCV000288604

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 8, 2016)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy.

Gerull B, Heuser A, Wichter T, Paul M, Basson CT, McDermott DA, Lerman BB, Markowitz SM, Ellinor PT, MacRae CA, Peters S, Grossmann KS, Drenckhahn J, Michely B, Sasse-Klaassen S, Birchmeier W, Dietz R, Breithardt G, Schulze-Bahr E, Thierfelder L.

Nat Genet. 2004 Nov;36(11):1162-4. Epub 2004 Oct 17. Erratum in: Nat Genet. 2005 Jan;37(1):106.

PubMed [citation]

PMID:: 15489853

Details of each submission

From OMIM, SCV000027342.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In 6 unrelated probands of western European descent, Gerull et al. (2004) found that arrhythmogenic right ventricular cardiomyopathy (609040) was related to a 235C-T transition in exon 2 of the PKP2 gene, causing an arg79-to-stop (R79X) mutation in the protein. At least 1 of the individuals had a positive family history and 1 had left ventricular as well as right ventricular involvement. All were male.

#	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		not provided	not provided	not provided	not provided

From Invitae, SCV000288604.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This sequence change creates a premature translational stop signal at codon 79 (p.Arg79*) of the PKP2 gene. It is expected to result in an absent or disrupted protein product. Truncating variants in PKP2 are known to be pathogenic (PMID: 15489853). This variant is clearly defined as a arrhythmogenic right ventricular cardiomyopathy causative allele (PMID: 21574009, 21606396). ClinVar contains an entry for this variant (Variation ID: 6754). For these reasons, this variant has been classified as Pathogenic.

#	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: Apr 7, 2017

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