Bleeding and platelet disorders

Gene: ADAMTS13

Green List (high evidence)

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 17 Oct 2023, 1:31 p.m. | Last Modified: 17 Oct 2023, 1:31 p.m.

Panel Version: 3.3

In accordance with Carl Fratter's review, it is recommended that ADAMTS13 should be made Green on Bleeding and platelet disorders panel, subject to the NHS Genomic Medicine Service approval.

Created: 17 Oct 2023, 1:29 p.m. | Last Modified: 17 Oct 2023, 1:29 p.m.

Panel Version: 3.2

Red List (low evidence)

Congenital Thrombotic Thrombocytopenic Purpura caused by homozygous or compound heterozygous variants is a disorder characterised by microvascular thrombosis. It is not appropriate to screen the ADAMTS13 gene in patients with bleeding and platelet disorders. ADAMTS13 is appropriatly listed as a gene in the R97 Thrombophilia gene panel.

Created: 14 Jun 2021, 2:17 p.m. | Last Modified: 14 Jun 2021, 2:17 p.m.

Panel Version: 1.26

Mode of inheritance
Other

Mode of pathogenicity
Other

Red List (low evidence)

The rating and mode of inheritance of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 8 Mar 2022, 10:48 a.m. | Last Modified: 8 Mar 2022, 10:48 a.m.

Panel Version: 1.35

This gene will be flagged for review at the next GMS panel update to highlight the recent review by Kate Downes (CUH) indicating that the phenotype associated with ADAMTS13 (MIM# 274150) may be out of scope for this panel (tagged Q2_21_expert_review)

Created: 30 Jun 2021, 11:09 a.m. | Last Modified: 30 Jun 2021, 11:13 a.m.

Panel Version: 1.26

Comment on mode of inheritance: Added MOI tag as this should be changed at the next GMS panel update from 'BOTH monoallelic and biallelic' to 'BIALLELIC'. Only biallelic cases with homozygous or compound heterozygous variants described. Heterozygous carriers are asymptomatic.

Created: 23 Mar 2021, 11:48 a.m. | Last Modified: 23 Mar 2021, 11:48 a.m.

Panel Version: 1.22

Green List (high evidence)

Gene rating submitted by Steve Keeney Molecular Diagnostics Centre Central Manchester NHS Foundation Trust January 2019 on behalf of North West GLH for the GMS Haematology specialist test group

Created: 18 Feb 2019, 11:23 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
274150 Thrombotic thrombocytopenic purpura, familial

Green List (high evidence)

Gene rating submitted by Mandy Nesbitt Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North East GLH for the GMS Haematology specialist test group.

Created: 13 Feb 2019, 11:32 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
274150 Thrombotic thrombocytopenic purpura, familial

Variants in this GENE are reported as part of current diagnostic practice

Green List (high evidence)

Gene rating submitted by Mike Mitchell Viapath St. Thomas' Hospital January 2019 on behalf of London South GLH for the GMS Haematology specialist test group.

Created: 7 Feb 2019, 1:21 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
274150 Thrombotic thrombocytopenic purpura, familial

Variants in this GENE are reported as part of current diagnostic practice

I don't know

Initial gene list (Consensus Genes for SPEC HAEM Panels 31.01.19 North West v1 FINAL.xlsx) collated by Steve Keeney Molecular Diagnostics Centre Central Manchester NHS Foundation Trust January 2019 on behalf of North West GLH for the GMS Haematology specialist test group. Gene Symbol submitted: ADAMTS13; Suggested initial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Phenotypes: 274150 Thrombotic thrombocytopenic purpura, familial; PMID(s): none submitted

Created: 18 Feb 2019, 11:28 a.m.

Initial gene list (Consensus Genes for Panels_Haem_SHEFFIELD-29.01.2019.xlsx) collated by Mandy Nesbitt Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North East GLH for the GMS Haematology specialist test group. Gene Symbol submitted: ADAMTS13; Suggested intial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? Yes; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Phenotypes: 274150 Thrombotic thrombocytopenic purpura, familial; PMID(s): none submitted

Created: 13 Feb 2019, 11:34 a.m.

Initial gene list (Consensus Genes for Panels_Bleeding and Thrombosis_South London.xlsx) collated by Mike Mitchell Viapath St. Thomas' Hospital January 2019 on behalf of London South GLH for the GMS Haematology specialist test group. Gene Symbol submitted: ADAMTS13; Suggested intial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? Yes; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Phenotypes: 274150 Thrombotic thrombocytopenic purpura, familial; PMID(s): none submitted

Created: 7 Feb 2019, 1:28 p.m.

Initial gene list (Consensus Genes for Panels 17.12.18_Haem_WWMGLH_v3.xlxs) collated by Carl Fratter Oxford Medical Genetics Laboratories January 2019 on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group. Gene Symbol submitted: ADAMTS13; Suggested intial gene rating: Green List (high evidence); Are variants in this gene as part of your current diagnostic practice? Yes; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal; Phenotypes: 274150 Thrombotic thrombocytopenic purpura, familial; PMID(s): 11586351; 12753286; 15009458

Created: 5 Feb 2019, 1:26 p.m.

Green List (high evidence)

Consensus opinion from the Central & South and South West haemostasis genomics MDT is that ADAMTS13 should be classified as a green gene on the R90 (bleeding and platelet disorders) panel. Laboratory findings in patients with congenital TTP include thrombocytopenia and this is not always readily distinguishable from other causes of thrombocytopenia.

Created: 3 May 2023, 2:29 p.m. | Last Modified: 3 May 2023, 2:29 p.m.

Panel Version: 3.2

Gene rating submitted by Carl Fratter Oxford Medical Genetics Laboratories January 2019 on behalf of Wessex and the West Midlands GLH for the GMS Haematology specialist test group.

Created: 5 Feb 2019, 11:19 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
274150 Thrombotic thrombocytopenic purpura, hereditary

Variants in this GENE are reported as part of current diagnostic practice