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Primary immunodeficiency

Gene: TBX1

Amber List (moderate evidence)

TBX1 (T-box 1)
EnsemblGeneIds (GRCh38): ENSG00000184058
EnsemblGeneIds (GRCh37): ENSG00000184058
OMIM: 602054, Gene2Phenotype
TBX1 is in 11 panels

7 reviews

Eleanor Williams (Genomics England Curator)

Comment on list classification: Changed rating of gene from Red to Amber. This gene was rated as Amber in v2.208 and incorrectly automatically demoted to Red in v2.209. This was due to a defect in the automatic PanelApp uploading tool when a set of publications was added to the panel with the source ‘Other’, and under certain conditions associated to previous sources listed, resulted in the rating of the gene being automatically changed when it should not have been.
Created: 14 Oct 2020, 12:17 p.m. | Last Modified: 14 Oct 2020, 12:17 p.m.
Panel Version: 2.216
The following PubMed IDs were added to entity TBX1: 12548732. These publications have been associated with OMIM phenotype MIM#188400, which is listed for this entity, by the immunodeficiencies subgroup of the Human Phenotype Ontology Immune Mediated Disorders Consortium (https://hpo-immune-mediated-disorders.groups.io/g/update) in August 2020.
Created: 13 Oct 2020, 9:36 a.m. | Last Modified: 13 Oct 2020, 9:36 a.m.
Panel Version: 2.208
Comment on list classification: After consultation with the Genomics England clinical team, keeping this gene as Amber. Further evidence is needed for the role of SNVs in TBX1 contributing to the PID phenotype.
Created: 19 Jun 2018, 9:35 a.m.
Comment on phenotypes: Added MIM identifier for DiGeorge Syndrome
Created: 14 Jun 2018, 2:16 p.m.
Comment on publications: Added publications relating to TBX1 variants and phenotypes
Created: 14 Jun 2018, 2:15 p.m.
In OMIM TBX1 is associated with DiGeorge Syndrome. Immunodeficiency is a clinical feature of this syndrome (Davies 2013 (PMID: 24198816)). Davies report that in 90% of cases of DiGeorge Syndrome have a typical 3 Mb deletion including over 30 different genes. There is some evidence that TBX1 is associated with the immunodeficiency phenotype. Yagi et al 2013 (PMID: 14585638) report on 13 patients from ten families who have the 22q11.2 syndrome phenotype (which includes DiGeorge Syndrome) but no detectable deletion of 22q11.2. Three new point mutations of TBX1 were discovered. These three mutations were not observed in 1110 normal, unrelated control chromosomes. Patient F2, with a point mutation resulting in a non-synonymous change G310S was diagnosed with DiGeorge's syndrome and his clinical phenotype included absent thymus suggesting a role for TBX1 in this phenotype. Jerome and Papaioannou, 2001 (PMID: 11242110) report that Tbx1-/- mice display a wide range of developmental anomalies including hypoplasia of the thymus. Overall there is not a strong degree of evidence from the literature that TBX1 variants alone are responsible for an immunodeficiency phenotype.
Created: 14 Jun 2018, 2:06 p.m.

Publications

Louise Daugherty (Genomics England Curator)

I don't know

OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): TBX1 .PanelApp HGNC gene symbol check: TBX1 . IUIS Disease: TBX1 deficiency . IUIS Inheritance: AD .T cells: N/A, .B cells: Normal, .IUIS Other affected cells: N/A. IUIS Associated features: Hypoparathyroidism, conotruncal cardiac malformation, velopalatal insufficiency, abnormal facies, intellectual disability. IUIS Major category: Combined immunodeficiencies with associated or syndromic features. IUIS Subcategory: Thymic Defects with Additional Congenital Anomalies
Created: 2 Jul 2018, 10:35 a.m.
This gene was present in the original PanelApp PID panel dataset (review in April 2018) rated as Red. The gene is present in the external expert immunodeficiency diagnostic gene list(s) GOSH or GRID. In this combined PID panel, this gene has been rated as AMBER and needs further curational review to assess pertinence prior to v1.
Created: 19 Apr 2018, 1:30 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: Del 22q11.2, PanelApp HGNC gene symbol check: TBX1, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Combined immunodeficiencies / Severe combined immunodeficiency (SCID) / Severe combined immunodeficiency (SCID); Other well defined PIDs / DiGeorge syndrome / DiGeorge syndrome
Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: TBX1, GRID_Gene_Symbol: TBX1, GRID_Transcript_ENS_Community submitted: ENST00000332710, GRID_Transcript_RefSeq: NM_080647.1, GRID_Transcript_ENS_used_on_Production: ENST00000332710
Created: 17 Apr 2018, 12:12 p.m.

Tracy Briggs (Manchester Genomic Medicine Centre)

Red List (low evidence)

Peter Arkwright (Royal Manchester Foundation Trust)

Red List (low evidence)

Ellen McDonagh (Genomics England Curator)

Comment on list classification: After reviewer ratings and comments, this should remain on the red list for now.
Created: 20 May 2016, 2:21 p.m.

Kimberly Gilmour (Great Ormond Street Hopsital)

I don't know

I would chose amber, we have seen it in several patients and functional as well as immunological data suggests real (patient lacks thymus but not 22q by array, missense mutation identified), but haven't published so at the moment the data isn't there.
Created: 20 Oct 2015, 1:47 p.m.

Sophie Hambleton (Newcastle University)

Red List (low evidence)

TBX1 is among the genes in the region 22q11.21 deleted in di George syndrome, which sometimes causes SCID. The aetiologic role of TBX1 in this phenotype is not known. OMIM provides a specific ID for di George syndrome, 188400
Created: 19 Oct 2015, 8:03 p.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Amber
  • Other
  • IUIS Classification December 2019
  • IUIS Classification February 2018
  • Victorian Clinical Genetics Services
  • ESID Registry 20171117
  • GRID V2.0
  • SCID v1.6
Phenotypes
  • Hypoparathyroidism, conotruncal cardiac malformation, velopalatal insufficiency, abnormal facies, intellectual disability
  • Di George syndrome
  • Severe combined immunodeficiency (SCID)
  • DiGeorge syndrome 188400
  • T-B+ SCID
  • Combined immunodeficiencies with associated or syndromic features
OMIM
602054
Clinvar variants
Variants in TBX1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

14 Oct 2020, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: tbx1 has been classified as Amber List (Moderate Evidence).

13 Oct 2020, Gel status: 1

Added New Source, Set publications, Status Update

Eleanor Williams (Genomics England Curator)

Source Other was added to TBX1. Publications for gene TBX1 were updated from 11242110; 14585638; 24198816; 32048120; 32086639 to 11242110; 32048120; 32086639; 14585638; 24198816; 12548732 Rating Changed from Amber List (moderate evidence) to Red List (low evidence)

28 Feb 2020, Gel status: 2

Added New Source, Set Phenotypes, Set publications

Louise Daugherty (Genomics England Curator)

Source IUIS Classification December 2019 was added to TBX1. Added phenotypes Hypoparathyroidism, conotruncal cardiac malformation, velopalatal insufficiency, abnormal facies, intellectual disability; Combined immunodeficiencies with associated or syndromic features for gene: TBX1 Publications for gene TBX1 were updated from 24198816; 14585638; 11242110 to 11242110; 14585638; 24198816; 32048120; 32086639

12 Jul 2018, Gel status: 2

Panel promoted to version 1.0

Louise Daugherty (Genomics England Curator)

2018-07-12 Louise Daugherty (Genomics England Curator) promoted panel to v1.0. Reviews were assessed, and panel was revised according to expert reviews and further in-house curation based on PanelApp guidelines. Previous panels (A- or hypo-gammaglobulinaemia, Congenital neutropaenia, Agranulocytosis, Combined B and T cell defect, Inherited complement deficiency and SCID panels) that were merged with this panel, were checked again for any changes/new reviews prior to versioning of this panel, these merged panels are now retired/made internal.

6 Jul 2018, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: tbx1 has been classified as Amber List (Moderate Evidence).

1 Jul 2018, Gel status: 2

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene TBX1 were set to T-B+ SCID, Di George syndrome, Severe combined immunodeficiency (SCID), DiGeorge syndrome 188400, Hypoparathyroidism, conotruncal cardiac malformation, velopalatal insufficiency, abnormal facies, intellectual disability, Combined immunodeficiencies with associated or syndromic features

26 Jun 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

IUIS Classification February 2018 was added to TBX1. Panel: Primary immunodeficiency disorders

26 Jun 2018, Gel status: 2

Added New Source

Louise Daugherty (Genomics England Curator)

Victorian Clinical Genetics Services was added to TBX1. Panel: Primary immunodeficiency disorders

19 Jun 2018, Gel status: 2

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: tbx1 has been classified as Amber List (Moderate Evidence).

14 Jun 2018, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: TBX1 were set to T-B+ SCID; Di George syndrome; Severe combined immunodeficiency (SCID); DiGeorge syndrome 188400

14 Jun 2018, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: TBX1 were set to T-B+ SCID; DiGeorge syndrome 188400; Severe combined immunodeficiency (SCID); DiGeorge syndrome

14 Jun 2018, Gel status: 2

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: TBX1 were set to 24198816; 14585638; 11242110

19 Apr 2018, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

17 Apr 2018, Gel status: 1

Added New Source, Set penetrance

Louise Daugherty (Genomics England Curator)

ESID Registry 20171117 was added to TBX1. Panel: Primary immunodeficiency disorders Phenotypes for gene TBX1 were set to T-B+ SCID, Di George syndrome, Severe combined immunodeficiency (SCID), DiGeorge syndrome

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene TBX1 were set to T-B+ SCID, Di George syndrome

17 Apr 2018, Gel status: 1

Added New Source, Set mode of inheritance, Set penetrance

Louise Daugherty (Genomics England Curator)

GRID V2.0 was added to TBX1. Panel: Primary immunodeficiency disorders Model of inheritance for gene TBX1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Phenotypes for gene TBX1 were set to T-B+ SCID, Di George syndrome

29 Mar 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

TBX1 was added to Primary immunodeficiency disorders panel. Sources: Expert Review Red, SCID v1.6

29 Mar 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

TBX1 was created by Louise Daugherty