ClinGen Dosage Sensitivity Curation Page
TBR1
- Curation Status: Complete
- id: ISCA-8312
- Date last evaluated: 2018-01-24
- Issue Type: ClinGen Gene Curation
- Gene type: protein-coding
- ClinGen: Search for information about TBR1 at clinicalgenome.org
- Entrez Gene: https://www.ncbi.nlm.nih.gov/gene/10716
- OMIM: https://omim.org/entry/604616
- ClinGen Haploinsufficiency Score: 3
- ClinGen Triplosensitivity Score: 0
- ExAC pLI score: 0.994
Select assembly:
(NC_000002.11)
(NC_000002.12)
- Haploinsufficiency score: 3
- Strength of Evidence (disclaimer): Sufficient evidence for dosage pathogenicity
- Haploinsufficiency Phenotype: Complex Neurodevelopmental Disorder
| 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.