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Primary immunodeficiency or monogenic inflammatory bowel disease v4.37 TLR7 Achchuthan Shanmugasundram Tag Q2_23_promote_green was removed from gene: TLR7.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.37 TLR7 Arina Puzriakova edited their review of gene: TLR7: Added comment: 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.; Changed rating: GREEN; Changed mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.36 TLR7 Achchuthan Shanmugasundram 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)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.22 TLR7 Achchuthan Shanmugasundram Tag Q2_23_promote_green tag was added to gene: TLR7.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.22 TLR7 Achchuthan Shanmugasundram Added comment: Comment on mode of pathogenicity: As reviewed by Boaz Palterer, gain-of-function variants are associated with systemic lupus erythematosus.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.22 TLR7 Achchuthan Shanmugasundram 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
Primary immunodeficiency or monogenic inflammatory bowel disease v4.21 TLR7 Achchuthan Shanmugasundram changed review comment from: 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.; to: 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.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.21 TLR7 Achchuthan Shanmugasundram Added comment: 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)".
Primary immunodeficiency or monogenic inflammatory bowel disease v4.21 TLR7 Achchuthan Shanmugasundram 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)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.20 TLR7 Achchuthan Shanmugasundram Classified gene: TLR7 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v4.20 TLR7 Achchuthan Shanmugasundram Added comment: 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.
Primary immunodeficiency or monogenic inflammatory bowel disease v4.20 TLR7 Achchuthan Shanmugasundram Gene: tlr7 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v4.19 TLR7 Achchuthan Shanmugasundram 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
Primary immunodeficiency or monogenic inflammatory bowel disease v4.18 TLR7 Achchuthan Shanmugasundram Publications for gene: TLR7 were set to 32706371
Primary immunodeficiency or monogenic inflammatory bowel disease v4.17 TLR7 Achchuthan Shanmugasundram reviewed gene: TLR7: Rating: GREEN; Mode of pathogenicity: None; Publications: 32706371, 35477763; Phenotypes: Systemic lupus erythematosus 17, OMIM:301080, Immunodeficiency 74, COVID19-related, X-linked, OMIM:301051; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Primary immunodeficiency or monogenic inflammatory bowel disease v2.548 TLR7 Boaz Palterer changed review comment from: Missense variants of TLR7 that are gain-of-function were shown to cause SLE in two kindreds and a single patient.
Extensive functional data and mice model.; to: 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.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.548 TLR7 Boaz Palterer reviewed gene: TLR7: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 35477763; Phenotypes: systemic lupus erythematosus, autoinflammatory, interferonopathy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Primary immunodeficiency or monogenic inflammatory bowel disease v2.526 TLR8 Zornitza Stark changed review comment from: PMID 34981838: Monozygotic male twins, hemizygous for the G572V (maternally inherited), who had severe autoimmune haemolytic anaemia (AIHA) worsening with infections, and autoinflammation presenting as fevers, enteritis, arthritis and CNS vasculitis. Functional showed variant causes impaired stability of the TLR8 protein, cross-reactivity to TLR7 ligands and reduced ability of TLR8 to attenuate TLR7 signaling.; to: PMID 34981838: Monozygotic male twins, hemizygous for the G572V (maternally inherited), who had severe autoimmune haemolytic anaemia (AIHA) worsening with infections, and autoinflammation presenting as fevers, enteritis, arthritis and CNS vasculitis. Functional showed variant causes impaired stability of the TLR8 protein, cross-reactivity to TLR7 ligands and reduced ability of TLR8 to attenuate TLR7 signaling.

Further evidence for germline variants causing disease.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.193 TLR7 Arina Puzriakova Classified gene: TLR7 as Amber List (moderate evidence)
Primary immunodeficiency or monogenic inflammatory bowel disease v2.193 TLR7 Arina Puzriakova Added comment: 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.
Primary immunodeficiency or monogenic inflammatory bowel disease v2.193 TLR7 Arina Puzriakova Gene: tlr7 has been classified as Amber List (Moderate Evidence).
Primary immunodeficiency or monogenic inflammatory bowel disease v2.184 TLR7 Zornitza Stark 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
Added comment: Four affected individuals from two unrelated families and some functional data.
Sources: Literature