ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000002.11) (NC_000002.12)
Evidence for haploinsufficiency phenotype
PubMed ID Description
24458984 Palumbo et al (2015) identified a de novo deletion by SNP array involving the entire TBR1 gene in an individual with slight dysmorphisms, skeletal alterations, and aggressive-impulsive behavior. Probes over flanking genes were not deviating.
25849321 Li et al (2016) used WES/WGS to identify a de novo frameshift variant in exon 1 of 6 of TBR1 in a patient with autism spectrum disorder and another de novo TBR1 frameshift in exon 6 (at amino acid 532) in a patient with intellectual disability.
23160955 O'Roak et al (2012) sequenced 44 candidate genes in 2,446 probands with autism spectrum disorder. They identified a de novo frameshift in exon 1 of TBR1 in one patient. This patient also had a rare, paternally-inherited duplication of at least 315 kb. Another patient was found to have a de novo frameshift in exon 4. Potentially de novo events were confirmed by Sanger sequencing in this study.

Haploinsufficiency phenotype comments:

PMID 25232744: Deriziotis et al performed functional studies on de novo TBR1 variants. One early frameshift was studied, which produced results consistent with loss-of-function. However, per the assays performed expression of the protein product was not reduced. PMID 24896178: c.1588_1594dupGGCTGCA frameshift at amino acid 532 reported as a de novo variant in a patient with intellectual disabiltiy. Appears to be the same variant reported by Li et al (2016).

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

Triplosensitivity phenotype comment:

No duplications involving only the TBR1 gene reported.