Dilated and arrhythmogenic cardiomyopathy
Gene: PPA2EnsemblGeneIds (GRCh38): ENSG00000138777
EnsemblGeneIds (GRCh37): ENSG00000138777
OMIM: 609988, Gene2Phenotype
PPA2 is in 12 panels
3 reviews
Eleanor Williams (Genomics England Curator)
The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.Created: 6 Dec 2024, 9:37 a.m. | Last Modified: 6 Dec 2024, 9:37 a.m.
Panel Version: 2.35
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Achchuthan Shanmugasundram (Genomics England Curator)
Comment on list classification: As reviewed by Matthew Edwards, there is sufficient evidence for this gene to be promoted to green rating at the next GMS review.Created: 8 Aug 2023, 5:46 p.m. | Last Modified: 8 Aug 2023, 5:46 p.m.
Panel Version: 2.14
PMID:34400813 reported 34 individuals from 20 unrelated families with rapidly progressive cardiac failure or sudden unexplained death in at least one family member and harboring biallelic PPA2 variants. Of these 34 individuals, only six remain alive and 23 died before the age of two. 12 individuals had dilated cardiomyopathy and nine had arrhythmia. The review of previous published reports showed there are four additional cases with dilated cardiomyopathy and eight additional cases with arrhythmia, bringing the total to 16 and 17 respectively.
This gene has been associated with relevant cardiac phenotypes in both OMIM (MIMs #617222 & #617223) and Gene2Phenotype (with 'definitive' rating in the DD panel).Created: 8 Aug 2023, 5:44 p.m. | Last Modified: 8 Aug 2023, 5:44 p.m.
Panel Version: 2.11
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Sudden cardiac failure, infantile, OMIM:617222; ?Sudden cardiac failure, alcohol-induced, OMIM:617223
Publications
Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)
Now a well established gene causing infantile sudden death, but can also manifest at a later age as alcohol-induced sudden death. Our lab and others have found several bi-allelic pathogenic variants in such SCD cases (see above ref). Is currently on syndromic/paediatric cardiomyopathy panel (R135) and mitochindrial panels, but wholly appropriate for this panel as well
Sources: Expert ReviewCreated: 9 Jun 2023, 3 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Sudden cardiac failure, infantile; Sudden cardiac failure, alcohol-induced
Publications
- PMID: 34400813
Variants in this GENE are reported as part of current diagnostic practice
Details
- Mode of Inheritance
- BIALLELIC, autosomal or pseudoautosomal
- Sources
-
- Expert Review Green
- NHS GMS
- Phenotypes
-
- Sudden cardiac failure, infantile, OMIM:617222
- ?Sudden cardiac failure, alcohol-induced, OMIM:617223
- OMIM
- 609988
- Clinvar variants
- Variants in PPA2
- Penetrance
- unknown
- Publications
- Panels with this gene
-
- Possible mitochondrial disorder - nuclear genes
- Fetal anomalies
- Dilated and arrhythmogenic cardiomyopathy
- Sudden death in young people
- Likely inborn error of metabolism
- Undiagnosed metabolic disorders
- Paediatric or syndromic cardiomyopathy
- Mitochondrial disorders
- Intellectual disability
- Childhood onset dystonia, chorea or related movement disorder
- DDG2P
- Congenital myopathy
History Filter Activity
Removed Tag, Removed Tag
Eleanor Williams (Genomics England Curator)Tag Q3_23_promote_green was removed from gene: PPA2. Tag Q3_23_NHS_review was removed from gene: PPA2.
Added New Source, Added New Source, Status Update
Eleanor Williams (Genomics England Curator)Source NHS GMS was added to PPA2. Source Expert Review Green was added to PPA2. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Entity classified by Genomics England curator
Achchuthan Shanmugasundram (Genomics England Curator)Gene: ppa2 has been classified as Amber List (Moderate Evidence).
Set Phenotypes
Achchuthan Shanmugasundram (Genomics England Curator)Phenotypes for gene: PPA2 were changed from Sudden cardiac failure, infantile; Sudden cardiac failure, alcohol-induced to Sudden cardiac failure, infantile, OMIM:617222; ?Sudden cardiac failure, alcohol-induced, OMIM:617223
Set publications
Achchuthan Shanmugasundram (Genomics England Curator)Publications for gene: PPA2 were set to PMID: 34400813
Added Tag, Added Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q3_23_promote_green tag was added to gene: PPA2. Tag Q3_23_NHS_review tag was added to gene: PPA2.
Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance
Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)gene: PPA2 was added gene: PPA2 was added to Dilated and arrhythmogenic cardiomyopathy. Sources: Expert Review Mode of inheritance for gene: PPA2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PPA2 were set to PMID: 34400813 Phenotypes for gene: PPA2 were set to Sudden cardiac failure, infantile; Sudden cardiac failure, alcohol-induced Penetrance for gene: PPA2 were set to unknown Review for gene: PPA2 was set to GREEN gene: PPA2 was marked as current diagnostic