Incidentalome

Gene: PKP2

reviewed by ClinGen Expert panel (published in 2021 PMID: 33831308) - DEFINITIVE

Created: 27 May 2021, 5:10 a.m. | Last Modified: 27 May 2021, 5:10 a.m.

Panel Version: 0.47

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Publications

• PMID: 33831308

Variants in this GENE are reported as part of current diagnostic practice

I don't know

Mutations in the PKP2 gene have been identified in individuals with arrhythmogenic right ventricular cardiomyopathy (ARVC). This condition most commonly affects the myocardium surrounding the right ventricle, one of the two lower chambers of the heart. ARVC increases the risk of an abnormal heartbeat (arrhythmia) and sudden death.

https://ghr.nlm.nih.gov/gene/PKP2
PMID:15489853, 16567567
https://doi.org/10.1371/journal.pone.0100560

ClinVar reports 1 variants only in an individual with DCM annotated as “LP” p.(His679Thr). No data regarding the variant associated with DCM is reported in GnomAD, supporting its low prevalence. However, if this is a variant linked to a clinical phenotype that initially manifested as ACM and then evolved into DCM is yet to be assessed. Considering that clinically cardiomyopathies are diseases with a progressive course, one cannot exclude that DCM cases carrying Pkp2 variants could be cases of advanced Arrythmogenic Cardiomyopathy (ACM or ARVC) which were missed in the initial disease phases. (https://doi.org/10.3389/fcvm.2018.00184)
Sources: Literature

Created: 5 Aug 2020, 6:39 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Arrhythmogenic right ventricular dysplasia 9 (MIM#609040)

Publications

• 15489853
• 16567567

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

PMID: 30562116: reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.

PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).

PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome.

Created: 7 Dec 2023, 3:55 a.m. | Last Modified: 7 Dec 2023, 3:55 a.m.

Panel Version: 0.296

DEFINITIVE by ClinGen.

Created: 3 Aug 2020, 7:08 a.m. | Last Modified: 3 Aug 2020, 7:08 a.m.

Panel Version: 0.29

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Arrhythmogenic right ventricular dysplasia 9, MIM# 609040; Dilated cardiomyopathy, MONDO:0005021, PKP2-related

Publications

• 30562116
• 35059364
• 38050058