Bleeding and platelet disorders

Gene: PTPN11

Amber List (moderate evidence)

PTPN11 (protein tyrosine phosphatase, non-receptor type 11)
EnsemblGeneIds (GRCh38): ENSG00000179295
EnsemblGeneIds (GRCh37): ENSG00000179295
OMIM: 176876, Gene2Phenotype
PTPN11 is in 30 panels

3 reviews

Steve Keeney (Central Manchester Foundation Trust)

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
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
163950 Noonan syndrome 1

Louise Daugherty (Genomics England Curator)

I don't know

Comment on list classification: After further discussion via email the GMS Haematology Specialist Test Group decided to rate PTPN11 Amber.
Created: 23 Sep 2019, 11:07 a.m. | Last Modified: 23 Sep 2019, 11:07 a.m.
Panel Version: 0.78
During the GMS Haematology Specialist Test Group webex call 8th March 2019 it was agreed to demote PRPN11 from Green to Red based on the syndromic phenotype (Noonan syndrome) would not present as bleeding/thrombocytopenia without other obvious symptoms.

Subsequent to this, a detailed review was recieved from Andrew Mumford (16th September 2019) : The clinical utility of the panel is to aid diagnosis of people presenting with bleeding or platelet disorders, where laboratory phenotype testing is insufficient for diagnosis. Noonan syndrome is about twice as common as haemophilia A, and can definitely present with coagulopathy with other features incompletely expressed of not recognised. These are all arguments to include PTPN11. Discovering Noonan syndrome is clinically important because of potential in interventions for other occult clinical features , like cardiac disease. However, we also have to be pragmatic here because using the same argument, there are dozens genes for other syndromic disorders which may present as a first contact in the bleeding disorders clinic (eg the EDS genes, CDG genes). We obviously shouldn’t be looking at all of these. The sensible option to me is to place carefully selected genes in this class ( i. associated with ‘common’ disorders and ii. in which other syndromic features may be less obvious to non-geneticists).

After this review, the gene was discussed again, and Carl Fratter and other members of the Haematology Specialist Test Group (Mandy Nesbit, Steve Keeny, Nicola Curry, Mike Mitchell agreed to change PTPN11 from Red to Amber rating, as this would then be in line with the Amber EDS genes on this panel.
Created: 23 Sep 2019, 11:07 a.m. | Last Modified: 23 Sep 2019, 11:07 a.m.
Panel Version: 0.77
Comment on list classification: As discussed in the GMS Haematology Specialist Test Group webex call 8th March 2019: The Specialist Test Group agreed that this gene should be rated Red so was downgraded from Green to Red. This gene is associated to Noonan syndrome
Created: 18 Mar 2019, 4:04 p.m.
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: PTPN11; Suggested initial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Phenotypes: 163950 Noonan syndrome 1; PMID(s): none submitted. Comment: ? Appropriate for this panel since Noonan's?
Created: 18 Feb 2019, 11:28 a.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: PTPN11; Suggested intial gene rating: Green List (high evidence); Are variants in this gene as part of your current diagnostic practice? No; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown; Phenotypes: 163950 Noonan syndrome 1; PMID(s): none submitted
Created: 5 Feb 2019, 1:26 p.m.

Carl Fratter (Oxford University Hospitals NHS Trust)

Green List (high evidence)

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.

History Filter Activity

23 Sep 2019, Gel status: 2

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: ptpn11 has been classified as Amber List (Moderate Evidence).

18 Mar 2019, Gel status: 1

Entity classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

Gene: ptpn11 has been classified as Red List (Low Evidence).

18 Feb 2019, Gel status: 4

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Added phenotypes 163950 Noonan syndrome 1 for gene: PTPN11

18 Feb 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source North West GLH was added to PTPN11.

5 Feb 2019, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to PTPN11.

5 Feb 2019, Gel status: 3

Added New Source, Set mode of inheritance, Set Phenotypes, Set publications, Status Update

Louise Daugherty (Genomics England Curator)

Source Expert Review Green was added to PTPN11. Mode of inheritance for gene PTPN11 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown Added phenotypes 163950 Noonan syndrome 1 for gene: PTPN11 Publications for gene PTPN11 were changed from to none submitted Rating Changed from Red List (low evidence) to Green List (high evidence)

5 Feb 2019, Gel status: 1

Created, Added New Source, Set mode of inheritance

Louise Daugherty (Genomics England Curator)

gene: PTPN11 was added gene: PTPN11 was added to Bleeding and platelet disorders. Sources: Wessex and West Midlands GLH Mode of inheritance for gene: PTPN11 was set to