RASopathies
Gene: MAP2K1

MAP2K1 (mitogen-activated protein kinase kinase 1)
EnsemblGeneIds (GRCh38): ENSG00000169032
EnsemblGeneIds (GRCh37): ENSG00000169032
OMIM: 176872, Gene2Phenotype
MAP2K1 is in 19 panels

3 reviews

Ivone Leong (Genomics England Curator)

Comment on publications: PMID: 23321623 (publication referring to Noonan syndrome association).
Created: 8 Oct 2020, 10:34 a.m. | Last Modified: 8 Oct 2020, 10:34 a.m.

Panel Version: 1.66

Created: 8 Oct 2020, 10:34 a.m.
Last Modified: 8 Oct 2020, 10:34 a.m.
Panel version: 1.66

Ellen McDonagh (Genomics England Curator)

Comment on mode of pathogenicity: Activating mutation consequence in G2P. Reviewer Comments: Gain of function mutations in MAP2K1 are responsible for up to 20% of cases of CFC. - Helen Savage (Congenica Ltd), Jan. 21, 2016, 10:31 a.m. Gain of function mutations in MAP2K1 cause Cardio-Facio-cutanenous syndrome and LEOPARD syndrome. These disorders share phenotypes with Legius syndrome. No reports of mutations in MAP2K1 causing Legius syndrome. - Helen Savage (Congenica Ltd), Jan. 25, 2016, 2:55 p.m. Gain of function mutations predicted to be associated with Noonan syndrome in fetuses with abnormal ultrasound findings (see PMID). Possible rare cause of Noonan syndrome; more commonly associated with Cardio-Facio-Cutaenous syndrome and LEOPARD syndrome. - Helen Savage (Congenica Ltd), Jan. 21, 2016, 2:01 p.m.
Created: 5 Feb 2016, 8:55 a.m.

Comment on mode of inheritance: Confirmed on G2P, and not on imprinted gene list.
Created: 5 Feb 2016, 8:48 a.m.

Comment on list classification: Confirmed DD gene for Cardiofaciocutaneous syndrome.
Created: 5 Feb 2016, 8:48 a.m.

Created: 5 Feb 2016, 8:48 a.m.

Panel version: 0.141

Helen Savage (Congenica Ltd)

Green List (high evidence)

Gain of function mutations
Created: 1 Feb 2016, 10:43 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Cardio-Facio-Cutaneous syndrome; LEOPARD syndrome

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Created: 1 Feb 2016, 10:43 a.m.

Panel version: 0.4

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Sources

Expert Review Green
Eligibility statement prior genetic testing
UKGTN
Radboud University Medical Center, Nijmegen

Phenotypes

Cardiofaciocutaneous syndrome 3, 615279
LEOPARD syndrome
?Noonan syndrome

OMIM

176872

Clinvar variants

Variants in MAP2K1

Penetrance

Complete

Publications

Mode of Pathogenicity

Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments

Panels with this gene

History Filter Activity

8 Oct 2020, Gel status: 3

Set Phenotypes

Ivone Leong (Genomics England Curator)

Phenotypes for gene: MAP2K1 were changed from Cardiofaciocutaneous syndrome 3; Cardiofaciocutaneous Syndrome; Cardio-Facio-Cutaneous syndrome; CFC syndrome; LEOPARD syndrome; ?Noonan syndrome to Cardiofaciocutaneous syndrome 3, 615279; LEOPARD syndrome; ?Noonan syndrome

8 Oct 2020, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: MAP2K1 were set to 21396583; 23321623 (publication referring to Noonan syndrome association).

8 Oct 2020, Gel status: 3

Set publications

Ivone Leong (Genomics England Curator)

Publications for gene: MAP2K1 were set to PMID: 21396583; 23321623 (publication referring to Noonan syndrome association).

5 Feb 2016, Gel status: 4