Paediatric or syndromic cardiomyopathy

Gene: TAB2

Green List (high evidence)

Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.

Created: 17 Jul 2023, 2:02 p.m. | Last Modified: 17 Jul 2023, 2:02 p.m.

Panel Version: 3.15

Review of 15 new patients from 13 families and 24 previously reported patients (PMID: 34741306) indicates that this gene is associated with cardiovascular heart disease, connective tissue disorder, and developmental delay. Structural heart defects are observed in most cases, particularly valvular defects and polyvalvular disease. 51% (20/39) of the cohort displayed a functional defect with dilated cardiomyopathy being the most frequent, observed in 46% (18/39) of individuals.

This link with congenital heart defects and cardiomyopathy has been replicated by other studies reporting SNVs and microdeletions (PMID: 28464518; 29700987; 32183715; 34456334; 36000780; 37153890). Although early reports indicated an association with non-syndromic CHD, more recent studies have shown that additional, extra-cardiac features are observed in majority of cases. Most variants are LoF with only a few missense variants reported.

Cardiomyocyte-specific deletion of Tab2 in mice (PMID: 34990405) triggered dilated cardiomyopathy with massive apoptotic and necroptotic cell death. Moreover, Tab2-deficient mice were also predisposed to myocardial injury and adverse remodelling after pathological stress.

Furthermore, an additional case in Genomics England's Clinical Variant Archive (CVA) dataset was identified via the Diagnostic Discovery initiative. The participant was recruited with dilated cardiomyopathy and a diagnostically reported LoF variant in this gene was returned, lending further support to adding this gene to the panel.

Created: 17 Jul 2023, 2 p.m. | Last Modified: 17 Jul 2023, 2 p.m.

Panel Version: 3.12

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Congenital heart defects, nonsyndromic, 2, OMIM:614980

Publications

• 28464518
• 29700987
• 32183715
• 34456334
• 34990405
• 34741306
• 36000780
• 37153890

Red List (low evidence)

Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Red on this panel.

Created: 2 Dec 2019, 3:58 p.m. | Last Modified: 2 Dec 2019, 3:58 p.m.

Panel Version: 0.16

I don't know

Limited evidence for association with congeital heart disease. Need more evidence.

Created: 26 Nov 2019, 5:42 p.m. | Last Modified: 26 Nov 2019, 5:42 p.m.

Panel Version: 0.13

Phenotypes
OMIM 614980 Congenital heart defects, nonsyndromic, 2

Publications

• 20493459

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 3 May 2024, 11:02 a.m. | Last Modified: 3 May 2024, 11:02 a.m.

Panel Version: 4.3

Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 4 nonsense variants reported in unrelated cases, as two cases with the same variant had dilated cardiomyopathy and two with different variants had aortic dilatation there is not sufficient for TAB2 to be green on this panel at the moment.

Created: 25 Jun 2019, 2:31 p.m. | Last Modified: 25 Jun 2019, 2:31 p.m.

Panel Version: 1.30

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown