NM_001005242.3(PKP2):c.1577del (p.Ala526fs) AND Arrhythmogenic right ventricular cardiomyopathy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Nov 15, 2010
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:: RCV000038180.5

Allele description [Variation Report for NM_001005242.3(PKP2):c.1577del (p.Ala526fs)]

NM_001005242.3(PKP2):c.1577del (p.Ala526fs)

Gene:

PKP2:plakophilin 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

12p11.21

Genomic location:

Preferred name:

NM_001005242.3(PKP2):c.1577del (p.Ala526fs)

HGVS:

NC_000012.12:g.32824142del
NG_009000.1:g.77705del
NM_001005242.3:c.1577delMANE SELECT
NM_004572.4:c.1709del
NP_001005242.2:p.Ala526fs
NP_004563.2:p.Ala570fs
LRG_398:g.77705del
NC_000012.11:g.32977076del
NC_000012.11:g.32977076delG
NM_004572.3:c.1709delC
c.1709delC
p.Ala570fs

Protein change:

A526fs

Links:

dbSNP: rs397517005

NCBI 1000 Genomes Browser:

rs397517005

Molecular consequence:

NM_001005242.3:c.1577del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004572.4:c.1709del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Arrhythmogenic right ventricular cardiomyopathy (ARVD)
Synonyms:: Cardiomyopathy, ARVC; Arrhythmogenic right ventricular dysplasia
Identifiers:: MONDO: MONDO:0016587; MedGen: C0349788

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000061847	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely pathogenic (Nov 15, 2010)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 16415378, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000061847

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Likely pathogenic
(Nov 15, 2010)

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	not provided	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Clinical expression of plakophilin-2 mutations in familial arrhythmogenic right ventricular cardiomyopathy.

Syrris P, Ward D, Asimaki A, Sen-Chowdhry S, Ebrahim HY, Evans A, Hitomi N, Norman M, Pantazis A, Shaw AL, Elliott PM, McKenna WJ.

Circulation. 2006 Jan 24;113(3):356-64. Epub 2006 Jan 16.

PubMed [citation]

PMID:: 16415378

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000061847.6

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

Description

The Ala570fs variant is predicted to cause a frameshift, which alters the protei n's amino acid sequence beginning at codon 570 and leads to a premature stop cod on 7 amino acids downstream. This alteration is then predicted to lead to a trun cated or absent protein (loss of function). Loss of function variants in the PKP 2 gene are common in patients with ARVC, increasing the likelihood that the Ala5 70fs variant is disease causing. In addition, the variant has been reported in one individual with a clinical diagnosis of ARVD/C as well as in the father, who was an obligate carrier. It was absent from 400 control chromosomes, supportin g a pathogenic role (Syrris 2006, please note that the authors refer to this var iant as Val570fs). In summary, the Ala570fs variant is likely pathogenic.

#	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: Dec 24, 2022

ClinVar

Relating variation to medicine