Dilated Cardiomyopathy and conduction defects

Gene: IDH2

Green List (high evidence)

IDH2 (isocitrate dehydrogenase (NADP(+)) 2, mitochondrial)
EnsemblGeneIds (GRCh38): ENSG00000182054
EnsemblGeneIds (GRCh37): ENSG00000182054
OMIM: 147650, Gene2Phenotype
IDH2 is in 12 panels

4 reviews

Rebecca Whittington (South West GLH)

Red List (low evidence)

D-2-hydroxyglutaric aciduria 2 OMIM:613657
Created: 25 Mar 2019, 4:30 p.m.
A feature can be dilated cardiomyopathy. Nota (J Med Genet. 2013 Nov;50(11):754-9. doi: 10.1136/jmedgenet-2013-101961) - two paediatric cases where first signs picked up prenatally on ultrasound, one of the two died of cardiac failure age 8 years. Kranendijk J Med Genet. 2013 Nov;50(11):754-9. doi: 10.1136/jmedgenet-2013-101961. - Variant at 140 assoc with this disorder. Note on HGMD only two variants in same nucleotide described. Akbay states cardiomyopathy requiring treatment is frequently observed in type II D2HGA patients (Kranendijk et al. 2010b, 2012). Note: 14 patients described in Kranendijk 2010 - 13 arisen denovo for the same variant Arg140Gln and also reported Arg140Gly in a patient.
Created: 25 Mar 2019, 4:27 p.m.
Paediatric onset only - paediatric panel
Created: 25 Mar 2019, 4:24 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Oxford Medical Genetics Laboratory (OUH NHS Foundation Trust)

Red List (low evidence)

Not fully reviewed however doesn't appear to be associated with primary non-syndromic teen/adult onset DCM.
Created: 17 Jan 2019, 5:41 p.m.

Ellen McDonagh (Genomics England Curator)

Comment on mode of inheritance: Changed from 'other' to monoallelic, due to reports of heterozygous variants to enable variants in this gene to be tiered.
Created: 5 May 2017, 7:40 a.m.

Sarah Leigh (Genomics England Curator)

Green List (high evidence)

Comment on mode of inheritance: >3 cases including PMID:20847235 who detected heterozygous germline variants in IDH2 that alter Arg140 in 15 unrelated patients with MIM:613657; in 14 cases the variant was de novo. The mother of 1 patient demonstrated germline mosaicism. PMID:24049096 also report a heterozygous IDH2 and the unaffected mother was a mosaic carrier. Somatic variants also reported.
Created: 20 Mar 2017, 12:23 p.m.
Inclusion of this as a green gene on this panel is appropriate, based on the review in the Undiagnosed metabolic disorders panel and the views of clinical expert, Dr Arianna Tucci, UCL.
Created: 20 Mar 2017, 12:22 p.m.

Mode of inheritance
Other

Phenotypes
D-2-hydroxyglutaric aciduria 2 613657

Publications

History Filter Activity

21 Feb 2019, Gel status: 4

Added New Source, Set mode of inheritance

Ellen McDonagh (Genomics England Curator)

Source South West GLH was added to IDH2. Mode of inheritance for gene IDH2 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

17 Jan 2019, Gel status: 3

Added New Source, Status Update

Ellen McDonagh (Genomics England Curator)

Source Wessex and West Midlands GLH was added to IDH2. Rating Changed from Green List (high evidence) to Green List (high evidence)

5 May 2017, Gel status: 4

Set Mode of Inheritance

Ellen McDonagh (Genomics England Curator)

Mode of inheritance for IDH2 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

5 May 2017, Gel status: 4

Set publications

Ellen McDonagh (Genomics England Curator)

Publications for IDH2 were set to 20847235;24049096

20 Mar 2017, Gel status: 4

Set Mode of Inheritance

Sarah Leigh (Genomics England Curator)

Mode of inheritance for IDH2 was changed to Other - please specifiy in evaluation comments

20 Mar 2017, Gel status: 4

Gene classified by Genomics England curator

Sarah Leigh (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

20 Mar 2017, Gel status: 0

Created

Sarah Leigh (Genomics England Curator)

IDH2 was created by sleigh

20 Mar 2017, Gel status: 0

Added New Source

Sarah Leigh (Genomics England Curator)

IDH2 was added to Dilated Cardiomyopathy and conduction defectspanel. Sources: Expert Review