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Paediatric or syndromic cardiomyopathy

Gene: POPDC2

Amber List (moderate evidence)

POPDC2 (popeye domain containing 2)
EnsemblGeneIds (GRCh38): ENSG00000121577
EnsemblGeneIds (GRCh37): ENSG00000121577
OMIM: 605823, Gene2Phenotype
POPDC2 is in 2 panels

3 reviews

Achchuthan Shanmugasundram (Genomics England Curator)

Green List (high evidence)

Comment on list classification: There are three unrelated individuals reported with both cardiac conduction disease and hypertrophic cardiomyopathy and identified with biallelic POPDC2 variants. Hence, this gene can be promoted to green rating in the next GMS update.
Created: 22 Apr 2026, 5:20 p.m. | Last Modified: 22 Apr 2026, 5:28 p.m.
Panel Version: 7.102
PMID:40409267 (2025) reported the identification of biallelic variants in POPDC2 gene in six patients from four families presenting with a phenotypic spectrum consisting of sinus node dysfunction, AV conduction defects, and hypertrophic cardiomyopathy. Hypertrophic cardiomyopathy was reported in two patients from two families (the only patient from family A and one of two patients from family B). Modelling and electrophysiological studies suggested effects of identified POPDC2 variants on cAMP binding and TREK-1 current.

PMID:41456958 (2026) reported the identification of a novel homozygous POPDC2 variant in a patient presenting with early-onset cardiac conduction disease and hypertrophic cardiomyopathy.

This gene has been associated with relevant phenotype in OMIM (MIM #621367, record last accessed on 22 April 2026), but not yet in Gene2Phenotype or ClinGen.
Created: 22 Apr 2026, 5:17 p.m. | Last Modified: 22 Apr 2026, 5:17 p.m.
Panel Version: 7.99

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cardiac conduction disease with or without cardiomyopathy 2, OMIM:621367; cardiac conduction disease with or without cardiomyopathy 2, MONDO:0700389

Publications

Ludmila Volozonoka (Children's Clinical University Hospital)

PMID: 41456958 presents additional biallelic LOF variant in a pediatric case presenting with arrhythmias and left ventricular hypertrophy.
Created: 23 Mar 2026, 3:38 p.m. | Last Modified: 23 Mar 2026, 3:38 p.m.
Panel Version: 7.99

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Dmitrijs Rots (Children's Clinical University Hospital)

Green List (high evidence)

PMID: 40409267 reports 4 families with recessive inheritance with presenting with cardiac conduction defects and hypertrophic cardiomyopathy with some functional evidence. enough for green rating.
Sources: Literature
Created: 23 Mar 2026, 9:31 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
cardiac conduction defects and hypertrophic cardiomyopathy

Publications

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Amber
Phenotypes
  • Cardiac conduction disease with or without cardiomyopathy 2, OMIM:621367
  • cardiac conduction disease with or without cardiomyopathy 2, MONDO:0700389
Tags
Q2_26_promote_green
OMIM
605823
Clinvar variants
Variants in POPDC2
Penetrance
unknown
Publications
Panels with this gene

History Filter Activity

22 Apr 2026, Gel status: 2

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: popdc2 has been classified as Amber List (Moderate Evidence).

22 Apr 2026, Gel status: 0

Set Phenotypes

Achchuthan Shanmugasundram (Genomics England Curator)

Phenotypes for gene: POPDC2 were changed from cardiac conduction defects and hypertrophic cardiomyopathy to Cardiac conduction disease with or without cardiomyopathy 2, OMIM:621367; cardiac conduction disease with or without cardiomyopathy 2, MONDO:0700389

22 Apr 2026, Gel status: 0

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: POPDC2 were set to PMID: 40409267

22 Apr 2026, Gel status: 0

Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q2_26_promote_green tag was added to gene: POPDC2.

23 Mar 2026, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Dmitrijs Rots (Children's Clinical University Hospital)

gene: POPDC2 was added gene: POPDC2 was added to Paediatric or syndromic cardiomyopathy. Sources: Literature Mode of inheritance for gene: POPDC2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POPDC2 were set to PMID: 40409267 Phenotypes for gene: POPDC2 were set to cardiac conduction defects and hypertrophic cardiomyopathy Penetrance for gene: POPDC2 were set to unknown Review for gene: POPDC2 was set to GREEN