Dilated Cardiomyopathy and conduction defects

Gene: PRDM16

Amber List (moderate evidence)

PRDM16 (PR/SET domain 16)
EnsemblGeneIds (GRCh38): ENSG00000142611
EnsemblGeneIds (GRCh37): ENSG00000142611
OMIM: 605557, Gene2Phenotype
PRDM16 is in 3 panels

4 reviews

Matthew Edwards (Clinical Genetics & Genomics Lab, Royal Brompton & Harefield NHS Trust)

I don't know

Paper by Arndt et al 2013 ( 24387996) described a minimal deleted region of exons 5-17 of PRDM16 as causative of the cardiomyopathy in 17/18 1p36 microdeletion syndrome patients; however the paper is refuted by de Leeuw & Houge 2014 (24387995).
DGV database has a relatively high number of deletion in control cases in this region.
some other cases with loss of function variants reported in literature assoc with DCM, but not enough evidence as yet.
Created: 8 Oct 2019, 11:35 a.m. | Last Modified: 8 Oct 2019, 11:35 a.m.
Panel Version: 1.63

Phenotypes
Cardiomyopathy, LVNC

Publications

Rebecca Whittington (South West GLH)

I don't know

Cardiomyopathy, dilated, 1LL OMIM#615373; Left ventricular noncompaction 8 OMIM#615373
Created: 25 Mar 2019, 4:30 p.m.
HGMD - DCM, LVNC and sudden death. Only 7 /21 variants classed as DM on HGMD, rare cause? 5 truncating variants on HGMD assoc with DCM or LVNC eg Meng (2017) ( JAMA Pediatr 171: 173438 PubMed: 28973083) de novo nonsense in a child in intensive care not clear if patient has DCM. Arndt (2013) Am J Hum Genet 93, 67) Seven variants detected four have freq, the two truncating variants look like they are pathogenic along with one missense but all are assoc with LVNC rather than DCM. This evidence was refuted by de Leeuw (2014) Am J Hum Genet 94: 153 PubMed: 24387995.
Created: 25 Mar 2019, 4:27 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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

Ellen McDonagh (Genomics England Curator)

I don't know

Comment on list classification: Promoted to Amber as not enough evidence at this stage to be Green.
Created: 20 Nov 2019, 10:31 a.m. | Last Modified: 20 Nov 2019, 10:31 a.m.
Panel Version: 1.64
This gene was part of an initial gene list collated by Matthew Edwards Royal Brompton Hospital sent 16th Jan 2019 on behalf of the London South GLH for review by the GMS Cardiology Specialist Group. Only gene symbol from the Royal Brompton gene panel was provided - suggested initial gene rating and evidence for inclusion not provided with the list.
Created: 20 Feb 2019, 2:17 p.m.

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

I don't know

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • South West GLH
  • London South GLH
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Cardiomyopathy, dilated, 1LL
OMIM
605557
Clinvar variants
Variants in PRDM16
Penetrance
Complete
Panels with this gene

History Filter Activity

20 Nov 2019, Gel status: 2

Entity classified by Genomics England curator

Ellen McDonagh (Genomics England Curator)

Gene: prdm16 has been classified as Amber List (Moderate Evidence).

21 Feb 2019, Gel status: 1

Added New Source, Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

Source South West GLH was added to PRDM16. Mode of inheritance for gene PRDM16 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

20 Feb 2019, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

Source London South GLH was added to PRDM16.

14 Jul 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

PRDM16 was added to Dilated Cardiomyopathy and conduction defectspanel. Sources: Radboud University Medical Center, Nijmegen