Ehlers Danlos syndromes

Gene: NOTCH1

Amber List (moderate evidence)

NOTCH1 (notch 1)
EnsemblGeneIds (GRCh38): ENSG00000148400
EnsemblGeneIds (GRCh37): ENSG00000148400
OMIM: 190198, Gene2Phenotype
NOTCH1 is in 14 panels

7 reviews

Ivone Leong (Genomics England Curator)

Comment on phenotypes: Previous phenotypes:
Connective Tissue Disorders;Aortic valve disease 1, 109730;Familial thoracic aortic aneurysm;Bicuspid, or bicommissural, aortic valve (BAV)
Created: 18 Mar 2021, 2:31 p.m. | Last Modified: 18 Mar 2021, 2:31 p.m.
Panel Version: 2.56

Eleanor Williams (Genomics England Curator)

I don't know

This gene was part of an initial gene list collated by Duncan Baker, Sheffield Diagnostic Genetics Service, January 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: NOTCH1; Suggested initial gene rating: red
Created: 3 Apr 2019, 3:41 p.m.

Duncan Baker (Sheffield Genetics)

Red List (low evidence)

Following discussion with Dr Diana Johnson - rate red
Created: 3 Apr 2019, 3:44 p.m.
No found any pathogenic mutations in service history. Phenotype not overlapping with EDS.
Created: 24 Jan 2019, noon

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Bicuspid, or bicommissural, aortic valve (BAV)

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

Helen Brittain (Genomics England Curator)

Red List (low evidence)

There is a clear gene-disease association (BAV) but in view of the relatively discrete vascular phenotype, this gene would be best placed on the FTAAD panel rather than as a differential diagnosis for those with connective tissue disease. Those with a vascular phenotype in addition would be offered the FTAAD panel in addition. D/W Neeti Ghali, EDS Specialist Clinic who is in agreement.
Created: 25 Jul 2017, 1:01 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Louise Daugherty (Genomics England Curator)

Comment on list classification: Changed from Green to Amber based due to the relatively discrete vascular phenotype
Created: 25 Jul 2017, 12:59 p.m.

Angela Brady (Nhs)

Green List (high evidence)

Neeti Ghali (NWTRGS, Northwick Park Hospital)

Green List (high evidence)

Associated with FTAA. Review from EDS National Diagnostic Service North West London Hospital NHS Trust: Dr Angela Brady FRCP PhD, Consultant Clinical Geneticist; Dr Neeti Ghali MBChB MD, Consultant Clinical Geneticist; Dr Fleur S van Dijk MD PhD, Consultant.
Created: 7 Jul 2017, 6:29 p.m.

History Filter Activity

18 Mar 2021, Gel status: 2

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: NOTCH1 were changed from Connective Tissue Disorders; Aortic valve disease 1, 109730; Familial thoracic aortic aneurysm; Bicuspid, or bicommissural, aortic valve (BAV) to connective tissue disease, MONDO:0003900

15 May 2019, Gel status: 2

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: NOTCH1 were changed from Connective Tissue Disorders; Aortic valve disease 1, 109730; Familial thoracic aortic aneurysm to Connective Tissue Disorders; Aortic valve disease 1, 109730; Familial thoracic aortic aneurysm; Bicuspid, or bicommissural, aortic valve (BAV)

13 Mar 2019, Gel status: 2

Added New Source

Eleanor Williams (Genomics England Curator)

Source NHS GMS was added to NOTCH1.

25 Jul 2017, Gel status: 2

panel promoted to version 1

Louise Daugherty (Genomics England Curator)

25 July 2017 Panel reviews were assessed, and panel was revised according to reviews and further curation.

25 Jul 2017, Gel status: 2

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Amber List (Moderate Evidence).

10 Jul 2017, Gel status: 4

Gene classified by Genomics England curator

Louise Daugherty (Genomics England Curator)

This gene has been classified as Green List (High Evidence).

10 Jul 2017, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for NOTCH1 were set to Connective Tissue Disorders; Aortic valve disease 1, 109730; Familial thoracic aortic aneurysm

10 Jul 2017, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for NOTCH1 were set to 17676603;26820064; 16729972

10 Jul 2017, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for NOTCH1 were set to Connective Tissue Disorders; Aortic valve disease 1, 109730

10 Jul 2017, Gel status: 1

Set publications

Louise Daugherty (Genomics England Curator)

Publications for NOTCH1 were set to 26820064; 16729972

28 Apr 2017, Gel status: 1

Set Mode of Inheritance

Louise Daugherty (Genomics England Curator)

Mode of inheritance for NOTCH1 was changed to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

28 Apr 2017, Gel status: 1

Set Phenotypes

Louise Daugherty (Genomics England Curator)

Phenotypes for NOTCH1 were set to Connective Tissue Disorders;Adams-Oliver syndrome 5, 616028

24 Jan 2017, Gel status: 0

Created

Ellen McDonagh (Genomics England Curator)

NOTCH1 was created by ellenmcdonagh

24 Jan 2017, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

NOTCH1 was added to Ehlers-Danlos syndromespanel. Sources: Expert list,Emory Genetics Laboratory