Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: SERPING1

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

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

Green List (high evidence)

Green List (high evidence)

Comment on mode of inheritance: OMIM states the association with Angioedema, hereditary, types I and II as both AR and AD

Created: 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 II

Created: 9 May 2018, 4:12 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Publications

• 1597123
• 7883978

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): 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/A

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, 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: ENST00000278407

Created: 17 Apr 2018, 12:12 p.m.