NM_001005242.3(PKP2):c.2065_2070delinsG (p.His689fs) AND Cardiomyopathy

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 3, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001171157.4

Allele description [Variation Report for NM_001005242.3(PKP2):c.2065_2070delinsG (p.His689fs)]

NM_001005242.3(PKP2):c.2065_2070delinsG (p.His689fs)

Gene:

PKP2:plakophilin 2 [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

12p11.21

Genomic location:

Preferred name:

NM_001005242.3(PKP2):c.2065_2070delinsG (p.His689fs)

HGVS:

NC_000012.12:g.32802500_32802505delinsC
NG_009000.1:g.99342_99347delinsG
NM_001005242.3:c.2065_2070delinsGMANE SELECT
NM_004572.4:c.2197_2202delinsG
NP_001005242.2:p.His689fs
NP_001005242.2:p.His689fs
NP_004563.2:p.His733fs
LRG_398:g.99342_99347delinsG
NC_000012.11:g.32955434_32955439delinsC
NM_001005242.2:c.2065_2070delinsG
NM_001005242.3:c.2065_2070delCACACCinsGMANE SELECT
NM_004572.3:c.2197_2202delCACACCinsG
NM_004572.4:c.2197_2202delinsG
c.2197_2202delinsG
p.H733AfsX8
p.His733AlafsX8
p.His733fs

Protein change:

H689fs

Links:

dbSNP: rs397517021

NCBI 1000 Genomes Browser:

rs397517021

Molecular consequence:

NM_001005242.3:c.2065_2070delinsG - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004572.4:c.2197_2202delinsG - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

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

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
SCV001333841	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 17, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004358855	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 3, 2023)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 16415378, 16549640, 19880068, 20152563, 20400443, 20857253, 22458570, 23812740, 27532257, 34469894, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001333841

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 17, 2021)

germline

clinical testing

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

SCV004358855

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 3, 2023)

germline

clinical testing

PubMed (11)
[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

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

Clinical features of arrhythmogenic right ventricular dysplasia/cardiomyopathy associated with mutations in plakophilin-2.

Dalal D, Molin LH, Piccini J, Tichnell C, James C, Bomma C, Prakasa K, Towbin JA, Marcus FI, Spevak PJ, Bluemke DA, Abraham T, Russell SD, Calkins H, Judge DP.

Circulation. 2006 Apr 4;113(13):1641-9. Epub 2006 Mar 20.

PubMed [citation]

PMID:: 16549640

See all PubMed Citations (11)

Details of each submission

From CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, SCV001333841.2

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

#	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

From Color Diagnostics, LLC DBA Color Health, SCV004358855.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

This variant deletes 5 nucleotides and inserts one nucleotide in exon 11 of the PKP2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in over 20 unrelated individuals affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 16415378, 16549640, 19880068, 20400443, 20152563, 20857253, 22458570, 23812740, 27532257, 34469894, 16415378, 34469894). It has been shown that this variant segregates with disease in multiple affected individuals across multiple families (PMID: 16415378, 34469894). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of PKP2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is 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: Feb 20, 2024

ClinVar

Relating variation to medicine