Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: C1S
agree with green geneCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
YES- this is covered on our targeted exomeCreated: 17 Sep 2019, 3:18 p.m. | Last Modified: 17 Sep 2019, 3:18 p.m.
Panel Version: 1.94
Autosomal dominant mutations in same gene cause Periodontal Ehlers Danlos syndrome, see PMID 27745832Created: 19 Jun 2018, 6:12 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
SLE; pyogenic infections
Publications
Added publication referenced by IUIS december 2019 updateCreated: 28 Feb 2020, 8:49 p.m. | Last Modified: 28 Feb 2020, 8:49 p.m.
Panel Version: 2.36
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): C1S .PanelApp HGNC gene symbol check: C1S . IUIS Disease: C1s deficiency . IUIS Inheritance: AR .T cells: Slightly increased DN T cells, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: SLE, infections with encapsulated organisms, Ehlers Danlos phenotype . IUIS Major category: Complement Deficiencies. IUIS Subcategory: N/ACreated: 2 Jul 2018, 10:35 a.m.
Comment on phenotypes: Added phenotypes suggested from external expert review.Created: 20 Jun 2018, 3:29 p.m.
Comment on publications: added publication PMID:18062908 suggested from external expert review to support upgrading of the gene to GreenCreated: 20 Jun 2018, 3:29 p.m.
Comment on list classification: Changed from Amber to Green due to expert review. It is noted that SLE; pyogenic infections are biallelic and that monoallelic forms result different phenotype, and this is reflected in the Ehlers-Danlos syndromes panelCreated: 20 Jun 2018, 3:28 p.m.
Keep Amber for now, more suitable for autoinflammatory spectrum panel? Seek external clinical review.Created: 15 Jun 2018, 3:24 p.m.
Past onto internal clinical team. The link between complement abnormalities and systemic lupus erythematosus (SLE) is well established and widely described. Homozygous and/or heterozygous complement-component deficiencies of the classical pathway (C1q, C1r, C1s, C4A, C4B and C2) are causally associated with susceptibility to the development of SLE- should this be reflected on this panel?Created: 15 Jun 2018, 2:14 p.m.
The incidence of SLE is 90% for C1q, 75% for C4, and 55% for C1r and C1s deficiency. This increased risk may be explained by that fact that C1q is important for the clearance of immune complexes and apoptotic cellsCreated: 15 Jun 2018, 1:56 p.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: 20 Apr 2018, 12:25 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: C1s, PanelApp HGNC gene symbol check: C1S, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Complement deficiencies / Complement deficiency / Complement component 1 deficiencyCreated: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: C1S, GRID_Gene_Symbol: C1S, GRID_Transcript_ENS_Community submitted: ENST00000328916, GRID_Transcript_RefSeq: NM_201442/NM_001734, GRID_Transcript_ENS_used_on_Production: ENST00000328916Created: 17 Apr 2018, 12:12 p.m.
Publications
Publications for gene C1S were updated from 11390518; 9856483; 20727163 to 27745832; 11390518; 20727163; 9856483
Source NHS GMS was added to C1S.
Source North West GLH was added to C1S.
Source London North GLH was added to C1S.
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.
Phenotypes for gene C1S were set to C1s deficiency, 613783, C1s deficiency, Lupus, Complement component 1 deficiency, SLE, pyogenic infections, SLE, infections with encapsulated organisms, Ehlers Danlos phenotype, Complement Deficiencies
IUIS Classification February 2018 was added to C1S. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to C1S. Panel: Primary immunodeficiency disorders
Gene: c1s has been classified as Green List (High Evidence).
Phenotypes for gene: C1S were set to C1s deficiency, 613783; C1s deficiency, Lupus; Complement component 1 deficiency; SLE; pyogenic infections
Publications for gene: C1S were set to 11390518; 9856483; 20727163
Gene: c1s has been classified as Green List (High Evidence).
Publications for gene: C1S were set to 11390518; 9856483; 20727163
Phenotypes for gene: C1S were set to C1s deficiency, 613783; C1s deficiency, Lupus; Complement component 1 deficiency
Expert Review Amber was added to C1S. Panel: Primary immunodeficiency disorders
ESID Registry 20171117 was added to C1S. Panel: Primary immunodeficiency disorders Phenotypes for gene C1S were set to C1s deficiency, Lupus, Complement component 1 deficiency
Phenotypes for gene C1S were set to C1s deficiency, Lupus
C1S was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
C1S was created by Louise Daugherty