Familial non syndromic congenital heart disease

Gene: TAB2

Comment on list classification: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. At least 4 nonsense variants reported in unrelated cases.
Watch list tag has been removed as sufficient variants have now been reported.

Created: 25 Jun 2019, 2:17 p.m. | Last Modified: 25 Jun 2019, 2:26 p.m.

Panel Version: 1.46

Green List (high evidence)

We've just reported a nonsense variant in a patient with complex congenital heart disease following clinical exome analysis. Bicuspid aortic valve, branch pulmonary stenosis, prolapsed mitral and tricuspid valves, small ASD

During the course of the variant review I found multiple examples of de novo Loss of Function variants in addition to the many gross deletions reported which include TAB2. PMID: 28135719 discusses de novo variants in developmental disorders and when checking via Decipher open access website (Patients 265804, 260227, 274309) the 3 nonsense variants included in this publication are present in patients who are all affected with congenital cardiac defects with or without short stature, minor dysmorphic facies and other features.

Created: 13 Mar 2019, 2:15 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

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

PMID: 28386937 - in Family 1, a novel heterozygous c.1398dup variant in this gene was identified in all affected family members. In Family 2, a de novo deletion of around 2Mb at chr6q25.1 was identified in the proband which includes the TAB2 gene. A review of previous cases is also provided in Tabe 1 of this publication - 22 patients have been reported with TAB2 variants, with variable phenotypes ranging from isolated congenital heart disease to systemic conditions with multiple malformations and intellectual disability/global developmental delay. Shared features include complex CHD with predominant valve involvement, short stature and facial dysmorphism.

Created: 14 Aug 2017, 2:29 p.m.

Publications

• 28386937

Comment when marking as ready: Recognised on G2P

Created: 30 Nov 2016, 12:09 p.m.

Only identified in two patients- one was a woman with left ventricular outflow tract obstruction, subaortic stenosis due to a fibromuscular shelf, residual aortic regurgitation, and atrial fibrillation. The other patient was a man with a bicuspid aortic valve and aortic dilation. Gene deletion identified in another family. De novo variants enriched in cohort with congenital heart disease

Created: 30 Nov 2016, 12:08 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Congenital heart defects, nonsyndromic, 2 614980

Publications

• 20493459, 26139517