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Primary immunodeficiency

Gene: TLR3

Green List (high evidence)

TLR3 (toll like receptor 3)
EnsemblGeneIds (GRCh38): ENSG00000164342
EnsemblGeneIds (GRCh37): ENSG00000164342
OMIM: 603029, Gene2Phenotype
TLR3 is in 5 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)

Eleanor Williams (Genomics England Curator)

Comment on mode of pathogenicity: Only missense variants reported to date
Created: 19 Jun 2018, 11:45 a.m.
Comment on publications: Added publication listing variants
Created: 19 Jun 2018, 11:36 a.m.
Comment on list classification: There are plausible disease-causing mutations identified in more than 3 families. All variants reported to date are missense.
Created: 19 Jun 2018, 11:32 a.m.
Changed penetrance to 'incomplete'
Created: 19 Jun 2018, 11:30 a.m.
Added 'missense' tag as all variants reported so far in exons are missense.
Created: 19 Jun 2018, 10:55 a.m.
In OMIM TLR3 is associated with {Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 2} and {HIV1 infection, resistance to}. 10 independent cases of missense variants in TLR3 in patients with herpes simplex encephalitis are reported by Zhang et al. (2007) (PMID: 17872438), Guo et al. (2011) (PMID: 21911422), Lim et al. (2014) (PMID: 25339207) and Mork et al. (2015) (26513235). Patients show a mixture of 1 heterozygous mutation, compound heterozygous mutations and homozygous mutation. Some family members of the two patients reported by Zhang et al. (2007) were also heterozygous for the mutation found, were HSV-1 seropositive but had not suffered from HSE suggesting that the mutation confers an autosomal dominant predisposition to the disease with incomplete penetrance. Lim et al (2014) also report dominant negative and haploinsufficiency effects. A review of literature finds a report by Sironi et al (2017) (PMID: 28368532) which describe a HSE patient with a previously reported variant (p.Leu297Val) and another with an intronic variant c.−8 + 6T > C, rs765240183), located 6 nucleotides downstream from the donor splice site of the first noncoding exon. All variants reported so far in exons are missense. Not in Gene2Phenotype. This gene should be rated green as there plausible disease-causing mutations identified in 3 or more families.
Created: 18 Jun 2018, 1:49 p.m.

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): TLR3 .PanelApp HGNC gene symbol check: TLR3 . IUIS Disease: TLR3 deficiency . IUIS Inheritance: AD or AR .T cells: N/A, .B cells: N/A, .IUIS Other affected cells: Central nervous system (CNS) resident cells and fibroblasts. IUIS Associated features: Herpes simplex virus 1 encephalitis (incomplete clinical penetrance for all etiologies listed here). IUIS Major category: Defects in Intrinsic and Innate Immunity. IUIS Subcategory: Herpes Simplex Encephalitis (HSE)
Created: 2 Jul 2018, 10:35 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, 12:30 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: TLR3, PanelApp HGNC gene symbol check: TLR3, 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: TLR3, GRID_Gene_Symbol: TLR3, GRID_Transcript_ENS_Community submitted: ENST00000296795, GRID_Transcript_RefSeq: NM_003265.2, GRID_Transcript_ENS_used_on_Production: ENST00000296795
Created: 17 Apr 2018, 12:12 p.m.

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • North West GLH
  • London North GLH
  • Expert Review Green
  • IUIS Classification February 2018
  • Victorian Clinical Genetics Services
  • Other
Phenotypes
  • Herpes simplex encephalitis, susceptibility to, 2
  • Herpetic encephalitis (HSE)
  • Herpes simplex virus 1 encephalitis (incomplete clinical penetrance for all etiologies listed here)
  • Defects in Intrinsic and Innate Immunity
Tags
missense
OMIM
603029
Clinvar variants
Variants in TLR3
Penetrance
Incomplete
Publications
Mode of Pathogenicity
Other - please provide details in the comments
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 TLR3.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to TLR3.

17 Sep 2019, Gel status: 3

Added New Source

Louise Daugherty (Genomics England Curator)

Source London North GLH was added to TLR3.

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 TLR3 were set to Herpes simplex encephalitis, susceptibility to, 2, Herpetic encephalitis (HSE), Herpes simplex virus 1 encephalitis (incomplete clinical penetrance for all etiologies listed here), Defects in Intrinsic and Innate Immunity

27 Jun 2018, Gel status: 4

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: tlr3 has been classified as Green List (High Evidence).

26 Jun 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

IUIS Classification February 2018 was added to TLR3. 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 TLR3. Panel: Primary immunodeficiency disorders

19 Jun 2018, Gel status: 3

Set mode of pathogenicity

Eleanor Williams (Genomics England Curator)

Mode of pathogenicity for gene: TLR3 was changed to Other - please provide details in the comments

19 Jun 2018, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: TLR3 were set to 21911422; 25339207; 25339207; 28368532

19 Jun 2018, Gel status: 3

Set mode of inheritance

Eleanor Williams (Genomics England Curator)

Mode of inheritance for gene: TLR3 was changed from Unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal

19 Jun 2018, Gel status: 3

Entity classified by Genomics England curator

Eleanor Williams (Genomics England Curator)

Gene: tlr3 has been classified as Green List (High Evidence).

19 Jun 2018, Gel status: 2

Removed Source, Removed Source, Added New Source, Set penetrance, Set penetrance

Eleanor Williams (Genomics England Curator)

Source GRID V2.0 was removed from TLR3. Panel: Primary immunodeficiency disorders Source ESID Registry 20171117 was removed from TLR3. Panel: Primary immunodeficiency disorders Other was added to TLR3. Panel: Primary immunodeficiency disorders Phenotypes for gene TLR3 were set to Herpes simplex encephalitis, susceptibility to, 2, Herpetic encephalitis (HSE) Penetrance for gene TLR3 was set to Incomplete

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 TLR3. Panel: Primary immunodeficiency disorders Phenotypes for gene TLR3 were set to Herpes simplex encephalitis, susceptibility to, 2, Herpetic encephalitis (HSE)

17 Apr 2018, Gel status: 1

Set penetrance

Louise Daugherty (Genomics England Curator)

Phenotypes for gene TLR3 were set to Herpes simplex encephalitis, susceptibility to, 2

17 Apr 2018, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

TLR3 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0

17 Apr 2018, Gel status: 1

Created

Louise Daugherty (Genomics England Curator)

TLR3 was created by Louise Daugherty