Primary immunodeficiency or monogenic inflammatory bowel disease

Gene: MAGT1

Comment on list classification: Changed rating of gene from Red to Green. This gene was rated as Green in v2.208 and incorrectly automatically demoted to Red in v2.209. This was due to a defect in the automatic PanelApp uploading tool when a set of publications was added to the panel with the source ‘Other’, and under certain conditions associated to previous sources listed, resulted in the rating of the gene being automatically changed when it should not have been.

Created: 14 Oct 2020, 1:20 p.m. | Last Modified: 14 Oct 2020, 1:20 p.m.

Panel Version: 2.275

The following PubMed IDs were added to entity MAGT1: 21796205;29635109. These publications have been associated with OMIM phenotype MIM#300853, which is listed for this entity, by the immunedysregulation subgroup of the Human Phenotype Ontology Immune Mediated Disorders Consortium (https://hpo-immune-mediated-disorders.groups.io/g/update) in August 2020.

Created: 13 Oct 2020, 9:36 a.m. | Last Modified: 13 Oct 2020, 9:36 a.m.

Panel Version: 2.208

Publications

• 21796205
• 29635109

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)

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): MAGT1 .PanelApp HGNC gene symbol check: MAGT1 . IUIS Disease: MAGT1 deficiency (XMEN) . IUIS Inheritance: XL .T cells: N/A, .B cells: Normal, .IUIS Other affected cells: N/A. IUIS Associated features: EBV infection, lymphoma, viral infections, respiratory and GI infections. IUIS Major category: Diseases of Immune Dysregulation. IUIS Subcategory: Susceptibility to EBV and Lymphoproliferative Conditions

Created: 2 Jul 2018, 10:35 a.m.

Transfer of reviews on publications that were in the publications section. Review made by Ellen McDonagh (Genomics England Curator), 3 Jun 2016. PMID: 21796205 - two young brothers with a 10bp deletion not present in the mother's cDNA or 100 normal individuals, present in the grandmother and great-grandmother of the patients. MAGT1 protein was undetectable in the patient's cells, screening of a third unrelated patient identified a nonsense mutation in exon 3 23846901 27095930 (2 patients with T-B+NK+ combined immunodeficiency) PMID: 25956530 case study of a 17 year old boy with severe autoimmune disorders and Hodgkin lymphoma mimicking autoimmune lymphoproliferative syndrome with a hemizygous c.555dup variant PMID: 25504528 case of a 58-year old Caucasian male and his nephew, identified novel variant c.712C > T, p.R238X (though unclear whether other unaffected family members had this variant) PMID: 25205404 clinical utility gene card describes 7 patients PMID: 24550228 - define XMEN disease, characterised by loss-of-function mutations in MAGT1. PMID: 23871722 association with X-linked intellectual disability is questioned PMID: 21983175 functional study

Created: 18 Apr 2018, 3:45 p.m.

Original metadata downloaded from ESID Registry. ESID_Gene_original: MAGT1, PanelApp HGNC gene symbol check: MAGT1, ESID classification: Main_category/ Sub_category/ PID_Diagnosis Combined immunodeficiencies / Combined immunodeficiency (CID) / Combined immunodeficiency

Created: 17 Apr 2018, 12:29 p.m.

Original metadata supplied by GRID. GRID Gene Symbol HGNC PanelApp check: MAGT1, GRID_Gene_Symbol: MAGT1, GRID_Transcript_ENS_Community submitted: ENST00000358075, GRID_Transcript_RefSeq: NM_032121.5, GRID_Transcript_ENS_used_on_Production: ENST00000358075

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

Green List (high evidence)

Comment on list classification: Added by an expert reviewer, with a second green review. Multiple cases reported for association with XMEN syndrome/disease.

Created: 3 Jun 2016, 2:47 p.m.

Green List (high evidence)

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Chronic active EBV, lymphoproliferation, combined immunodeficiency, impaired t cell function

Publications

• Mg2+ regulates cytotoxic functions of NK and CD8 T cells in chronic EBV infection through NKG2D.Science. 2013 Jul 12
• 341(6142):186-91