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Primary immunodeficiency

Gene: TBK1

Green List (high evidence)

TBK1 (TANK binding kinase 1)
EnsemblGeneIds (GRCh38): ENSG00000183735
EnsemblGeneIds (GRCh37): ENSG00000183735
OMIM: 604834, Gene2Phenotype
TBK1 is in 7 panels

5 reviews

Kimberly Gilmour (Great Ormond Street Hopsital)

Green List (high evidence)

agree with green gene
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94

Tracy Briggs (Manchester Genomic Medicine Centre)

Green List (high evidence)

YES- this is covered on our targeted exome
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94

Sophie Hambleton (Newcastle University)

Green List (high evidence)

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

Eleanor Williams (Genomics England Curator)

Green List (high evidence)

Comment on list classification: Rating this gene green as there are 3 unrelated cases with a likely pathogenic mutation in this gene.
Created: 5 Jun 2018, 4:45 p.m.
In OMIM this gene is associated with Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8. OMIM reports 3 independent cases in which variants in this gene are thought to cause this phenotype. Firstly, Herman et al. (2012)(PMID: 22851595) report of 2 unrelated patients from Poland and France with herpes simplex encephalitis , Herman et al. (2012) identified heterozygous missense mutations in the TBK1 gene (G159A and D50A). Both are loss of function mutations (loss of kinase activity (G159A) and protein instability (D50A)). In vitro functional expression assays showed that the G159A mutation had a dominant-negative effect, whereas the D50A mutation resulted in haploinsufficiency. Neither variant was found in dbSNP (build 135) or in 1050 control human DNA samples. OMIM also cite Mork et al. (2015) (PMID: 26513235), who report a Danish woman (P10) with adult-onset herpes simplex encephalitis with a heterozygous missense mutation in the TBK1 gene (I207V). The variant was confirmed by Sanger sequencing, was not found in the ExAC database. No data about this gene in Gene2Phenotype. Rating this gene green as there are 3 unrelated cases with a likely pathogenic mutation in this gene.
Created: 5 Jun 2018, 4:43 p.m.
Comment on phenotypes: Added {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8}
Created: 5 Jun 2018, 3:12 p.m.

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

Publications

Louise Daugherty (Genomics England Curator)

Green List (high evidence)

Gene rating submitted by Kimberly Gilmour and Austen Worth on behalf of London North GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email 6th September the Specialist Test Group all agreed there is enough evidence to rate this gene Green.
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Gene rating submitted by Tracy Briggs, David Gokhale and Abigal Rousseau on behalf of North West GLH for the GMS Immunology specialist test group. As discussed with the GMS Immunology Specialist Test Group during webex call 28th March 2019 and confirmed in follow up email on 20th June the Specialist Test Group all agreed there is enough evidence to rate this gene Green.
Created: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
OriginaI Metadata from IUIS classification table (February, 2018) downloaded 20180614. IUIS Genetic defect (original gene symbol in IUIS download): TBK1 .PanelApp HGNC gene symbol check: TBK1 . IUIS Disease: TBK1 deficiency . IUIS Inheritance: AD .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: CNS resident cells and fibroblasts. IUIS Associated features: Herpes simplex virus 1 encephalitis. IUIS Major category: Defects in Intrinsic and Innate Immunity. IUIS Subcategory: Herpes Simplex Encephalitis (HSE)
Created: 2 Jul 2018, 10:35 a.m.
Comment on mode of inheritance: added MOI from external expert review
Created: 13 Jun 2018, 10:23 a.m.
Comment on publications: added to support upgrading of the gene to Green
Created: 13 Jun 2018, 10:22 a.m.
This gene was absent from the original PanelApp PID panel dataset (review April 2018). However it was listed in 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, 1:34 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: TBK1, PanelApp HGNC gene symbol check: TBK1, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Defects in innate immunity / Herpetic encephalitis / Herpetic encephalitis (HSE)
Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: TBK1, GRID_Gene_Symbol: TBK1, GRID_Transcript_ENS_Community submitted: ENST00000331710, GRID_Transcript_RefSeq: NM_013254.3, GRID_Transcript_ENS_used_on_Production: ENST00000331710
Created: 17 Apr 2018, 12:12 p.m.

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • NHS GMS
  • North West GLH
  • London North GLH
  • IUIS Classification February 2018
  • Victorian Clinical Genetics Services
  • Expert Review Green
  • ESID Registry 20171117
  • GRID V2.0
Phenotypes
  • Herpes simplex encephalitis, susceptibility to
  • Herpetic encephalitis (HSE)
  • {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8} 617900
  • Herpes simplex virus 1 encephalitis
  • Defects in Intrinsic and Innate Immunity
OMIM
604834
Clinvar variants
Variants in TBK1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to TBK1.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to TBK1.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to TBK1.

12 Jul 2018, Gel status: 4

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.

1 Jul 2018, Gel status: 4

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene TBK1 were set to Herpes simplex encephalitis, susceptibility to, Herpetic encephalitis (HSE), {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8} 617900, Herpes simplex virus 1 encephalitis, Defects in Intrinsic and Innate Immunity

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

IUIS Classification February 2018 was added to TBK1. Panel: Primary immunodeficiency disorders

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Victorian Clinical Genetics Services was added to TBK1. Panel: Primary immunodeficiency disorders

13 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: tbk1 has been classified as Green List (High Evidence).

13 Jun 2018, Gel status: 3

Set mode of inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for gene: TBK1 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

13 Jun 2018, Gel status: 3

Set publications

Louise Daugherty (Genomics England Curator)

Publications for gene: TBK1 were set to 22851595; 26513235

5 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: tbk1 has been classified as Green List (High Evidence).

5 Jun 2018, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: TBK1 were set to Herpes simplex encephalitis, susceptibility to; Herpetic encephalitis (HSE); {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8} 617900

5 Jun 2018, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: TBK1 were set to Herpes simplex encephalitis, susceptibility to; Herpetic encephalitis (HSE); {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8} 617900

5 Jun 2018, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: TBK1 were set to Herpes simplex encephalitis, susceptibility to; Herpetic encephalitis (HSE); {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 8} 617900

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 TBK1. Panel: Primary immunodeficiency disorders Phenotypes for gene TBK1 were set to Herpes simplex encephalitis, susceptibility to, Herpetic encephalitis (HSE)

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene TBK1 were set to Herpes simplex encephalitis, susceptibility to

17 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

TBK1 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0

17 Apr 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

TBK1 was created by Louise Daugherty