ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000018.9) (NC_000018.10)
Evidence for haploinsufficiency phenotype
PubMed ID Description
16962354 El-Jaick et al. (2007) sequenced TGIF1 in 435 individuals with HPE and detected 4 mutations in TGIF1, including a de novo nonsense mutation. The authors also recapitulate the functional studies by Gripp et al. (2000).
12522553 Aguilella et al. (2003) sequenced TGIF1 in 127 HPE individuals and found 2 mutations, including 1 nonsense mutation. The nonsense mutation was inherited from a father with hypotelorism and cleft lip, microsigns of HPE, but no ID.
22125506 Keaton et al. report seven individuals with mutations or deletions (large or focal) involving TGIF1 and also summarize data from other publications. Two frameshift LOF mutations (p.Phe86Serfs*13, p.Arg260Glyfs*58) and one "focal gene deletion" found in this study alone.

Haploinsufficiency phenotype comments:

PMID:10835638: Gripp et al. (2000) sequenced TGIF1 in 268 individuals with HPE and found 4 heterozygous missense mutations. One of these mutations (S28C) was also seen in the father and grandfather of the proband, both of whom had ocular hypotelorism, a microsign of HPE, suggesting this mutation segregates with the phenotype. A de novo P36R mutation was described and functional studies of the mutant protein indicated decreased binding to the TGIF1 target site and loss of transcriptional regulatory activity in multiple assays. The other mutations were not as well characterized. PMID: Mutations in TGIF1 display incomplete penetrance and variable expressivity.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity

Triplosensitivity phenotype comment:

No Identified Literature.