Primary immunodeficiency or monogenic inflammatory bowel disease
Gene: SERPING1
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
Comment on mode of inheritance: OMIM states the association with Angioedema, hereditary, types I and II as both AR and ADCreated: 14 May 2018, 8:32 p.m.
Comment on list classification: Making green as there is enough evidence for variants in this gene being association with the disorder, and GeL clinicians agree that it is an autoinflammatory disorder within scope of this expanded panel.Created: 14 May 2018, 8:30 p.m.
In OMIM this gene (with the previous symbol of C1NH) is associated with "Angioedema, hereditary, types I and II" and "Complement component 4, partial deficiency of". Genetics Home Reference explains that Angioedema, hereditary, types I and II is thought to be caused by mutations in the SERPING1 gene which provides instructions for making the C1 inhibitor protein, which is important for controlling inflammation. OMIM reports that patients with HAE type I (absent or low levels of an antigenically-normal protein) appear to have a deletion of the C1 inhibitor gene or a truncated transcript because of a stop codon, whereas patients with HAE type II (elevated or normal levels of a dysfunctional protein) have a single base substitution (Davis et al., 1992; Cicardi and Agostoni, 1996). Numerous studies are reported in OMIM describing cases where either point mutations or large deletions are found in patients with Angioedema, hereditary, types I and II. In particular Roche et al., 2005 (PMID: 1597123) report on 87 Spanish families (77 with type I, and 10 with type II HAE). They found large rearrangements in 13 families, and point mutations or microdeletions/insertions in 74 families. Only one case of SERPING1 involvement with 'Complement component 4, partial deficiency of' has been reported. This was by Zahedi et al 1995 (PMID: 7883978) who reports that in 11 members of a 5-family kindred spanning 3 generations an ala443-to-val mutation in the C1NH ( SERPING1) gene, resulting in a dysfunctional C1 inhibitor. The pattern of inheritance was autosomal dominant.Created: 10 May 2018, 10:08 a.m.
Comment on phenotypes: Added phenotype of Complement component 4, partial deficiency of 120790 and added MIM number to Angioedema, hereditary, types I and IICreated: 9 May 2018, 4:12 p.m.
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications
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): SERPING1 .PanelApp HGNC gene symbol check: SERPING1 . IUIS Disease: C1 inhibitor deficiency . IUIS Inheritance: AD .T cells: Normal, defective TCR mediated activation, .B cells: N/A, .IUIS Other affected cells: N/A. IUIS Associated features: Hereditary angioedema. IUIS Major category: Complement Deficiencies. IUIS Subcategory: N/ACreated: 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, 3:18 p.m.
Original metadata downloaded from ESID Registry. ESID_Gene_original: C1 Inhibitor, PanelApp HGNC gene symbol check: SERPING1, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Complement deficiencies / Complement deficiency / Hereditary Angioedema (C1inh)Created: 17 Apr 2018, 12:29 p.m.
Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: SERPING1, GRID_Gene_Symbol: SERPING1, GRID_Transcript_ENS_Community submitted: ENST00000278407, GRID_Transcript_RefSeq: NM_000062.2, GRID_Transcript_ENS_used_on_Production: ENST00000278407Created: 17 Apr 2018, 12:12 p.m.
Source NHS GMS was added to SERPING1.
Source North West GLH was added to SERPING1.
Source London North GLH was added to SERPING1.
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 SERPING1 were set to Angioedema, hereditary, types I and II 106100, Hereditary Angioedema (C1inh), Complement component 4, partial deficiency of 120790, Hereditary angioedema, Complement Deficiencies
IUIS Classification February 2018 was added to SERPING1. Panel: Primary immunodeficiency disorders
Victorian Clinical Genetics Services was added to SERPING1. Panel: Primary immunodeficiency disorders
Gene: serping1 has been classified as Green List (High Evidence).
Publications for gene: SERPING1 were set to 1597123; 7883978
Mode of inheritance for SERPING1 was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Mode of inheritance for SERPING1 was changed from MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
This gene has been classified as Green List (High Evidence).
This gene has been classified as Green List (High Evidence).
Phenotypes for SERPING1 were set to Angioedema, hereditary, types I and II 106100; Hereditary Angioedema (C1inh); Complement component 4, partial deficiency of 120790
Phenotypes for SERPING1 were set to Angioedema, hereditary, types I and II 106100; Hereditary Angioedema (C1inh); Complement component 4, partial deficiency of 120790
This gene has been classified as Amber List (Moderate Evidence).
ESID Registry 20171117 was added to SERPING1. Panel: Primary immunodeficiency disorders Phenotypes for gene SERPING1 were set to Angioedema, hereditary, types I and II, Hereditary Angioedema (C1inh)
Phenotypes for gene SERPING1 were set to Angioedema, hereditary, types I and II
SERPING1 was added to Primary immunodeficiency disorders panel. Sources: GRID V2.0
SERPING1 was created by Louise Daugherty