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Intellectual disability

Gene: TBR1

Green List (high evidence)

TBR1 (T-box, brain 1)
EnsemblGeneIds (GRCh38): ENSG00000136535
EnsemblGeneIds (GRCh37): ENSG00000136535
OMIM: 604616, Gene2Phenotype
TBR1 is in 5 panels

3 reviews

Konstantinos Varvagiannis (Other)

I don't know

Vegas et al. (PMID: 30268909) report on 2 unrelated individuals with the same frameshift variant in TBR1 [NM_006593.3:c.1588_1594dup, p.(Thr532Argfs*144)] occurring as a de novo event. Both presented with similar phenotype including frontal pachygyria as well as severe intellectual disability. One of these individuals was already described in the context of a larger ID cohort (de Ligt et al. - PMID: 23033978).

The authors cite previous studies with other TBR1 mutation-positive patients (10 in total, 5 of whom with de novo variants) and a diagnosis of ID/ASD investigated in the context of larger cohorts (PMIDs: 25356899, 23160955, 22495311 and others).

Overall, most variants reported are missense (within the T Box domain) with few loss-of-function ones.

TBR1 is included in gene panels for intellectual disability offered by different diagnostic laboratories.

Functional characterization of 3 missense TBR1 variants previously reported in patients with neurodevelopmental disorder supports severe disruption of TBR1 function for some but not all these variants(all predicted pathogenic in silico) [PMID: 30250039].

This gene could possibly be rated as amber until further and better characterized cases are published.
Created: 14 Nov 2018, 10:21 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Intellectual disability; Autism; Abnormal cortical gyration

Publications

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

Caroline Wright (Sanger)

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
AUTISM

Publications

Lu Raymond (university of cambridge )

Green List (high evidence)

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
Phenotypes
  • AUTISM
OMIM
604616
Clinvar variants
Variants in TBR1
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

29 Sep 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source Victorian Clinical Genetics Services was added to TBR1.

12 Mar 2018, Gel status: 3

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 0

Added New Source

Ellen McDonagh (Genomics England Curator)

TBR1 was added to Intellectual disabilitypanel. Sources: Expert Review Green

13 Nov 2015, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

TBR1 was created by ellenmcdonagh