Description
RASopathies Eligibility (29373.1)

Relevant diseases:
- Noonan syndrome
- Noonan syndrome plus other features - Cardio-facio-cutaneous syndrome
- LEOPARD syndrome
- Costello syndrome
- Legius syndrome

RASopathies Inclusion
- At least 2 of the suggestive clinical features: - Early feeding difficulty/ failure to thrive
- Relative macrocephaly
- Short stature
- Developmental disability
- At least 1 of:
- Cardiomyopathy
- Congenital heart disease
- Arrhythmia
- Suggestive malignancy ( bladder carcinoma, Rhabdomyosarcoma, Leukaemia, phaeochromocytoma)
- Skin abnormalities (hyperkeratosis, caf├® au lait patches, ulerythema oophorogenes, keratosis pilaris, excess
palmar skin)

RASopathies Exclusion Criteria
- Low birth weight for gestation
Prior Genetic Testing:
- Results should have been reviewed for all genetic tests undertaken. This includes review of available exome sequencing data, but where this is the case can be limited to genes specified within disease-relevant in silico panels. The patient is not eligible if a pathogenic variant has been identified in any gene related to their phenotype.
- Standard local genetic testing and nationally commissioned testing for this phenotype should have been completed AND
- Testing should be undertaken for any individual gene for which diagnostic yield is >10% for this phenotype AND
- The following specific gene tests are advised as a means of limiting the re-discovery of recognised pathogenic variants that could be more efficiently identified through the existing catalogue of UKGTN tests:

RASopathy Prior Testing Prior Testing Prior Testing Prior Testing Prior Testing Prior Testing Genes
- PTPN11, RAF1, BRAF, SOS1, KRAS, HRAS, NRAS, SHOC2, CBL, SPRED1, MAP2K1, MAP2K2

These requirements will be kept under continual review during the main programme and may be subject to change.

6 reviewers

  • Ellen McDonagh (Genomics England Curator)

    Group: other
    Workplace: other

  • Andrea Haworth (ACGS, Congenica)

    Group: Other biotech or pharmaceutical
    Workplace: Other clinical service

  • Helen Savage (Congenica Ltd)

    Group: Other biotech or pharmaceutical
    Workplace: Other clinical service

  • Ellen Thomas (Genomics England Curator)

    Group: Other
    Workplace: Other

  • Rebecca Foulger (Genomics England curator)

    Group: Other
    Workplace: Other

  • Alice Gardham (Genomics England)

    Group: Other
    Workplace: Other

19 genes

19 reviewed, 17 green

List Gene Reviews Mode of inheritance Details
19 genes
Green Green List (high evidence)
BRAF
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Eligibility statement prior genetic testing
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
Phenotypes
  • LEOPARD Syndrome
  • Noonan Syndrome
  • Cardiofaciocutaneous Syndrome
  • LEOPARD syndrome 3
  • Cardio-facio-cutaneous syndrome
Green Green List (high evidence)
CBL
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Eligibility statement prior genetic testing
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Illumina TruGenome Clinical Sequencing Services
Phenotypes
  • Noonan syndrome-like disorder with or without juvenile myelomonocytic leukemia
Green Green List (high evidence)
HRAS
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • UKGTN
  • Radboud University Medical Center, Nijmegen
  • Eligibility statement prior genetic testing
Phenotypes
  • Costello syndrome
Green Green List (high evidence)
KRAS
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
  • Eligibility statement prior genetic testing
Phenotypes
  • Noonan syndrome 3
  • Noonan syndrome
  • Cardiofaciocutaneous syndrome 2
  • Cardiofaciocutaneous Syndrome
  • Cardio-Facio-Cutaneous syndrome
  • CFC syndrome
Green Green List (high evidence)
LZTR1
3 reviews
2 green
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Expert Review
Phenotypes
  • Noonan syndrome 10
  • Prenatal hydrops
  • increased nuchal translucency
  • cardiac findings
Green Green List (high evidence)
MAP2K1
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • UKGTN
  • Eligibility statement prior genetic testing
  • Radboud University Medical Center, Nijmegen
  • Expert Review Green
Phenotypes
  • Cardiofaciocutaneous syndrome 3
  • Cardiofaciocutaneous Syndrome
  • Cardio-Facio-Cutaneous syndrome
  • CFC syndrome
  • LEOPARD syndrome
  • ?Noonan syndrome
Green Green List (high evidence)
MAP2K2
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • UKGTN
  • Emory Genetics Laboratory
  • Eligibility statement prior genetic testing
Phenotypes
  • Cardiofaciocutaneous syndrome 4
  • Cardio-Facio-Cutaneous syndrome type 4
  • Cardiofaciocutaneous Syndrome
  • Cardio-Facio-Cutaneous syndrome
  • CFC syndrome
Green Green List (high evidence)
NF1
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Neurofibromatosis-Noonan Syndrome
  • Neurofibromatosis Noonan syndrome
  • Noonan syndrome
  • Neurofibromatosis syndrome 1
Green Green List (high evidence)
NRAS
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • UKGTN
  • Eligibility statement prior genetic testing
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Noonan syndrome
  • Noonan syndrome 6
  • Cardio-Facio-cutanenous syndrome
  • CFC Syndrome
Green Green List (high evidence)
PPP1CB
1 review
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Other
  • Expert Review Green
Phenotypes
  • Noonan syndrome-like disorder with loose anagen hair 2, 617506
  • Rasopathy with developmental delay, short stature and sparse slow-growing hair
Green Green List (high evidence)
PTPN11
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Emory Genetics Laboratory
  • Illumina TruGenome Clinical Sequencing Services
  • Expert Review Green
  • UKGTN
  • Eligibility statement prior genetic testing
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • LEOPARD syndrome
  • LEOPARD syndrome 1
  • Noonan syndrome
  • Noonan syndrome 1
Green Green List (high evidence)
RAF1
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • UKGTN
  • Eligibility statement prior genetic testing
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Noonan syndrome
  • Noonan syndrome 5
  • LEOPARD syndrome
  • LEOPARD syndrome 2
Green Green List (high evidence)
RIT1
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Noonan syndrome 8
  • Noonan syndrome type 8
Green Green List (high evidence)
SHOC2
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • UKGTN
  • Eligibility statement prior genetic testing
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Noonan-like syndrome with loose anagen hair
Green Green List (high evidence)
SOS1
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • UKGTN
  • Eligibility statement prior genetic testing
  • Illumina TruGenome Clinical Sequencing Services
  • Emory Genetics Laboratory
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Noonan syndrome
  • Noonan syndrome 4
Green Green List (high evidence)
SOS2
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Sources
  • Expert Review Green
  • Expert Review
Phenotypes
  • Noonan syndrome 9
Tags
  • curated-variant-list
Green Green List (high evidence)
SPRED1
2 reviews
1 green
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Green
  • UKGTN
  • Eligibility statement prior genetic testing
  • Radboud University Medical Center, Nijmegen
  • Emory Genetics Laboratory
Phenotypes
  • Legius Syndrome
  • Neurofibromatosis-like syndrome
Red Red List (low evidence)
A2ML1
2 reviews
1 red
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Red
Phenotypes
  • Noonan syndrome
Red Red List (low evidence)
RASA2
1 review
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Other
Phenotypes
  • Noonan syndrome?

0 STRs

0 reviewed, 0 green

List STR Reviews Mode of inheritance Details
0 STRss

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