Neurofibromatosis Type 1 (Version 1.32)

Description

Neurofibromatosis Type 1 eligibility statement:

Neurofibromatosis Type 1 inclusion criteria (38878)
A.	Proband with a clinically confirmed diagnosis of Neurofibromatosis type 1, OR
B.	Proband with multiple café-au-lait patches but no non-pigmentary features

Where the NF1 gene has not been tested before recruitment, participants should be recruited initially as singletons. In families where analysis as a singleton does not lead to identification of the underlying causative mutations, recruitment of additional affected family members is encouraged.

Neurofibromatosis Type 1 exclusion criteria (38878)

Prior genetic testing guidance (38878)
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. 
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.  

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Neurofibromatosis Type 1 prior genetic testing genes (38878)
Testing as below is strongly recommended PRIOR TO RECRUITMENT to allow appropriate management of families with readily detectable mutations in known disease genes:
- In case A above (clinically confirmed diagnosis of NF1) prior testing as below is strongly recommended to allow appropriate management.
- In case B above (no non-pigmentary features) testing of the following genes should be considered but is not required prior to recruitment:
NF1

Closing statement (38878)
These requirements will be kept under continual review during the main programme and may be subject to change.

Panel Activity

10 reviewers

Ellen McDonagh (Genomics England Curator)

Group: Other
Workplace: Other
Helen Savage (Congenica Ltd)

Group: Other biotech or pharmaceutical
Workplace: Other clinical service
Helen Lindsay (Leeds Genetics Laboratory)

Group: Other NHS organisation
Workplace: NHS diagnostic lab
Mark Greenslade (Bristol Genetics Laboratory)

Group: Other NHS organisation
Workplace: NHS diagnostic lab
Rebecca Foulger (Genomics England curator)

Group: Other
Workplace: Other
Alice Gardham (Genomics England)

Group: Other
Workplace: Other
Louise Daugherty (Genomics England Curator)

Group: Other
Workplace: Other
Helen Brittain (Genomics England Curator)

Group: Other
Workplace: Other
Arina Puzriakova (Genomics England Curator)

Group: Other
Workplace: Other
Achchuthan Shanmugasundram (Genomics England Curator)

Group: Other
Workplace: Other

31 Entities

31 reviewed, 25 green

List	Entity	Reviews	Mode of inheritance	Details
Filter Entities 31 Entitiess
Green Green List (high evidence)	BRAF	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Emory Genetics Laboratory Expert Review Expert Review Green Illumina TruGenome Clinical Sequencing Services Literature Radboud University Medical Center, Nijmegen Phenotypes Noonan syndrome with multiple lentigines (LEOPARD syndrome), 151100 Tags
Green Green List (high evidence)	BRCA2	3 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Fanconi anemia, complementation group D1, OMIM:605724 Tags
Green Green List (high evidence)	BRIP1	3 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Fanconi anemia, complementation group J, OMIM:609054 Tags
Green Green List (high evidence)	FANCA	3 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Fanconi anemia, complementation group A, 227650 Fanconi Anemia Fanconi Anaemia Tags
Green Green List (high evidence)	FANCB	4 reviews 3 green	X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)	Sources Emory Genetics Laboratory Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Fanconi anemia, complementation group B, 300514 Fanconi Anemia, X-Linked Fanconi Anemia Type B Fanconi Anaemia Tags
Green Green List (high evidence)	FANCC	3 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Fanconi anemia, complementation group C, 227645 Fanconi Anemia Fanconi Anaemia Tags
Green Green List (high evidence)	FANCD2	3 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Fanconi anemia, complementation group D2, 227646 Fanconi Anemia Fanconi Anaemia Tags
Green Green List (high evidence)	FANCE	3 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Fanconi anemia, complementation group E, 600901 Fanconi Anemia Fanconi Anaemia Tags
Green Green List (high evidence)	FANCF	3 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Fanconi anemia, complementation group F, 603467 Fanconi Anemia Fanconi Anaemia Tags
Green Green List (high evidence)	FANCG	3 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Fanconi anemia, complementation group G, 614082 Fanconi Anemia Fanconi Anaemia Tags
Green Green List (high evidence)	FANCI	3 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Fanconi anemia, complementation group I, 609053 Fanconi Anemia Fanconi Anaemia Tags
Green Green List (high evidence)	FANCL	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Fanconi anemia, complementation group L, 614083 Fanconi Anemia Fanconi Anaemia Tags
Green Green List (high evidence)	GNAS	3 reviews 1 green 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green UKGTN Phenotypes McCune-Albright syndrome, somatic, mosaic, OMIM:174800 panostotic fibrous dysplasia, MONDO:0043168 Tags mosaicism
Green Green List (high evidence)	17q11.2 recurrent region (includes NF1) Loss ISCA-37431-Loss Region	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources ClinGen Expert Review Green Phenotypes dysmorphic features, cardiac anomalies and mental retardation 613675 variable facial dysmorphism, cafe-au-lait spots, neurofibromas and Lisch nodules in the iris, mental retardation, developmental delay, an excessive number of early-onset neurofibromas and an increased risk for malignant peripheral nerve sheath tumors NEUROFIBROMATOSIS 1 MICRODELETION SYNDROME NF1 MICRODELETION SYNDROME Chromosome 17q11.2 deletion syndrome, 1.4Mb Tags
Green Green List (high evidence)	KITLG	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Literature Phenotypes Hyperpigmentation with or without hypopigmentation, 145250 Tags
Green Green List (high evidence)	MLH1	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Expert Review Green Illumina TruGenome Clinical Sequencing Services UKGTN Phenotypes Mismatch repair cancer syndrome, 276300 Tags
Green Green List (high evidence)	MSH2	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Expert Review Green Illumina TruGenome Clinical Sequencing Services UKGTN Phenotypes Mismatch repair cancer syndrome, 276300 Tags
Green Green List (high evidence)	MSH6	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Expert Review Green Illumina TruGenome Clinical Sequencing Services UKGTN Phenotypes Mismatch repair cancer syndrome, 276300 Tags
Green Green List (high evidence)	NF1	3 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Eligibility statement prior genetic testing Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Neurofibromatosis, familial spinal Familial Spinal Neurofibromatosis Neurofibromatosis, type 1 Neurofibromatosis-Noonan syndrome Watson syndrome, 162200 Tags
Green Green List (high evidence)	PALB2	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Fanconi anemia, complementation group N, 610832 {Breast cancer, susceptibility to}, 114480 {Pancreatic cancer, susceptibility to, 3}, 613348 Fanconi Anemia Fanconi Anaemia Tags
Green Green List (high evidence)	PMS2	1 review 1 green	BIALLELIC, autosomal or pseudoautosomal	Sources Emory Genetics Laboratory Expert Review Expert Review Green Illumina TruGenome Clinical Sequencing Services UKGTN Phenotypes Mismatch repair cancer syndrome, 276300 Tags
Green Green List (high evidence)	PTPN11	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Green UKGTN Phenotypes Noonan syndrome with multiple lentigines (LEOPARD syndrome), 151100 Tags
Green Green List (high evidence)	RAF1	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Expert Review Green Literature UKGTN Phenotypes Noonan syndrome with multiple lentigines (LEOPARD syndrome), 151100 Tags
Green Green List (high evidence)	SLX4	4 reviews 4 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Fanconi anemia, complementation group P, 613951 Fanconi Anemia Fanconi Anaemia Tags
Green Green List (high evidence)	SPRED1	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Green UKGTN Phenotypes Legius syndrome, 611431 Tags
Amber Amber List (moderate evidence)	POLA1	1 review	X-LINKED: hemizygous mutation in males, biallelic mutations in females	Sources Expert Review Amber Literature Phenotypes Pigmentary disorder, reticulate, with systemic manifestations, X-linked, 301220 XLPDR Tags non-coding-known-pathogenic
Amber Amber List (moderate evidence)	RAD51C	5 reviews 2 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Amber Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Fanconi anemia, complementation group O, 613390 {Breast-ovarian cancer, familial, susceptibility to, 3}, 613399 Fanconi Anemia Fanconi Anaemia Tags watchlist
Red Red List (low evidence)	ERCC4	4 reviews 3 green	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Radboud University Medical Center, Nijmegen UKGTN Phenotypes Xeroderma pigmentosum, group F, 278760 XFE progeroid syndrome, 610965 Fanconi anemia, complementation group Q, 615272 Xeroderma pigmentosum, type F/Cockayne syndrome, 278760 Fanconi Anaemia Tags
Red Red List (low evidence)	FANCM	6 reviews 2 green 1 red	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Fanconi anemia, complementation group M, 614087 Fanconi Anemia Fanconi Anaemia Tags
Red Red List (low evidence)	MAP2K1	1 review 1 red	MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted	Sources Expert Review Red Literature Phenotypes Noonan syndrome with multiple lentigines (LEOPARD syndrome), 151100 Tags
Red Red List (low evidence)	UBE2T	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Red Illumina TruGenome Clinical Sequencing Services Literature Phenotypes Fanconi anaemia, complementation group T, 616435 Tags

Neurofibromatosis Type 1 (Version 1.32)

10 reviewers

31 Entities

31 reviewed, 25 green

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