Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: TLR7
Comment on mode of pathogenicity: As reviewed by Boaz Palterer, gain-of-function variants are associated with systemic lupus erythematosus.Created: 18 May 2023, 12:48 p.m. | Last Modified: 18 May 2023, 12:48 p.m.
Panel Version: 4.22
Comment on mode of inheritance: There are three cases and supporting functional evidence available for systemic lupus erythematosus caused by X-linked dominant variants. However, there are only two unrelated cases in support of COVID19-related immunodeficiency caused by X-linked recessive variants. Hence, the MOI should be updated from "X-LINKED: hemizygous mutation in males, biallelic mutations in females" to "X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)".Created: 18 May 2023, 12:46 p.m. | Last Modified: 18 May 2023, 12:46 p.m.
Panel Version: 4.21
Comment on list classification: As reviewed by Boaz Palterer, there are three unrelated cases and functional evidence from mouse models in support of the association of X-linked dominant variants from TLR7 gene to systemic lupus erythematosus. Hence, this gene can be promoted to GREEN rating at the next major update.Created: 18 May 2023, 12:40 p.m. | Last Modified: 18 May 2023, 12:46 p.m.
Panel Version: 4.21
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Systemic lupus erythematosus 17, OMIM:301080; Immunodeficiency 74, COVID19-related, X-linked, OMIM:301051
Publications
Missense variants of TLR7 that are gain-of-function (p.Y264H, p.F507L and p.R28G) were shown to cause SLE in two kindreds and a single patient.
Extensive functional data and mice model.Created: 4 May 2022, 11:47 a.m. | Last Modified: 4 May 2022, 11:50 a.m.
Panel Version: 2.548
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
systemic lupus erythematosus; autoinflammatory; interferonopathy
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
The rating of this gene has been updated to Green and the mode of inheritance set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) following NHS Genomic Medicine Service approval.Created: 11 Oct 2023, 12:54 p.m. | Last Modified: 11 Oct 2023, 12:54 p.m.
Panel Version: 4.37
Comment on list classification: Phenotype is more relevant to a severe COVID-19 clinical course - this gene is already Green on the COVID-19 research panel (Version 1.69).
Therefore, rating Amber, but this can be reviewed if new evidence emerges.Created: 18 Sep 2020, 2:08 p.m. | Last Modified: 18 Sep 2020, 2:08 p.m.
Panel Version: 2.193
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Four affected individuals from two unrelated families and some functional data.
Sources: LiteratureCreated: 7 Sep 2020, 10:02 p.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes
Immunodeficiency 74, COVID19-related, X-linked, MIM# 301051
Publications
Tag Q2_23_promote_green was removed from gene: TLR7.
Source Expert Review Green was added to TLR7. Source NHS GMS was added to TLR7. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q2_23_promote_green tag was added to gene: TLR7.
Mode of pathogenicity for gene: TLR7 was changed from None to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mode of inheritance for gene: TLR7 was changed from X-LINKED: hemizygous mutation in males, biallelic mutations in females to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Gene: tlr7 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: TLR7 were changed from Immunodeficiency 74, COVID19-related, X-linked, MIM# 301051 to Systemic lupus erythematosus 17, OMIM:301080; Immunodeficiency 74, COVID19-related, X-linked, OMIM:301051
Publications for gene: TLR7 were set to 32706371
Gene: tlr7 has been classified as Amber List (Moderate Evidence).
gene: TLR7 was added gene: TLR7 was added to Primary immunodeficiency. Sources: Literature Mode of inheritance for gene: TLR7 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: TLR7 were set to 32706371 Phenotypes for gene: TLR7 were set to Immunodeficiency 74, COVID19-related, X-linked, MIM# 301051 Review for gene: TLR7 was set to GREEN