TOF_TBX1
- Gene
- TBX1
- Disease
- TOF
- Inheritance
- AD
- Classification
- Limited
- Total Score
- 2
- Publications Reviewed
- 2
- Publication Span
- 4.58 years
- Last Updated
- 08/18/2025
- Curator(s)
- Macayla Weiner, Laurel Hiatt
Description
TBX1_TOF curation is based on one tetralogy of Fallot (ToF) proband with a heterozygous 30-bp polyalanine expansion in TBX1 (c.1399-1428dup30) reported in a 230-patient ToF cohort. The proband had ToF with absent pulmonary valve, isolated left pulmonary artery, additional VSD, scoliosis, and limited extracardiac features; functional testing showed severely reduced transcriptional activity and protein aggregation. Gene-level mouse Tbx1 timed-deletion studies support roles in pharyngeal and cardiovascular development, including aortic arch and outflow tract defects, but are not tandem-repeat/locus-specific.
Genetic evidence
Total: 1
| Singular Evidence | Probands | PMID:19948535 | 1 | One female proband from a 230-patient ToF cohort carried TBX1 c.1399-1428dup30, an in-frame 30-bp polyalanine expansion; the variant was absent in 185 controls, mother was negative, and father was unavailable. Phenotype included ToF with absent pulmonary valve, isolated left pulmonary artery, additional VSD, scoliosis, and no 22q11.2-typical facial gestalt; functional testing showed severely reduced transcriptional activity and protein aggregation, but segregation was unavailable. |
Experimental evidence
Total: 1
| Models | Non-human model organism | PMID:16141220 | 1 | Gene-level, not tandem-repeat/locus-specific: timed conditional Tbx1 deletion in mouse embryos caused pharyngeal and cardiovascular developmental defects, including aortic arch patterning and outflow tract abnormalities; the study supports Tbx1 developmental function but does not model the human TBX1 polyalanine repeat expansion. |
Note: Maximum score caps apply at evidence type, category, and supercategory levels, so section totals may be lower than the raw sum of row scores.