RASopathies
Gene: HRAS
Gain-of-Function variants, including a newly described duplication: HRAS c.186_206dup p.(Glu62_Arg68dup) (reference: https://doi.org/10.1038/s41431-020-0662-4)Created: 15 Nov 2020, 6:02 p.m. | Last Modified: 15 Nov 2020, 6:02 p.m.
Panel Version: 1.73
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
hypertrophic cardiomyopathy; Chiari 1 malformation; ectodermal findings
Publications
Mode of pathogenicity
Other
Comment on mode of pathogenicity: Comments from Reviewer: Gain of function variants cause Costello syndrome. Gain of function mutations in HRAS cause Costello syndrome. No strong association with Noonan syndrome or other 'RASopathies'. - Helen Savage (Congenica Ltd), Jan. 21, 2016, 4:13 p.m. Gain of function variants cause Costello syndrome. No reported association with Legius syndrome. - Helen Savage (Congenica Ltd), Jan. 22, 2016, 12:18 p.m.Created: 5 Feb 2016, 12:11 p.m.
Comment on mode of inheritance: Confirmed on G2P and OMIM. Not on imprinted gene list. Comment from Reviewer: Gain of function mutations in HRAS are known to cause Costello syndrome. The majority of these mutations are de novo in the proband. Inheritance from a somatic mosaic parent has been observed (PMID: 19206176). - Helen Savage (Congenica Ltd), Jan. 21, 2016, 10:49 a.m.Created: 5 Feb 2016, 8:45 a.m.
Comment on list classification: Confirmed DD gene for Costello syndrome.Created: 5 Feb 2016, 8:39 a.m.
Gain of function mutationsCreated: 1 Feb 2016, 10:44 a.m.
Gain of function mutationsCreated: 1 Feb 2016, 10:42 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Publications for gene: HRAS were set to 16170316; 16969868; 16443854; 21396583
Phenotypes for gene: HRAS were changed from Costello syndrome to Costello syndrome, 218040
Publications for gene: HRAS were set to PMID: 16170316; 16969868; 16443854; 21396583
Publications for HRAS were set to PMID: 16170316; 16969868; 16443854; 21396583
This gene has been classified as Green List (High Evidence).
Publications for HRAS were set to PMID: 16170316; 16969868; 16443854
Phenotypes for HRAS were set to Costello syndrome
Mode of pathogenicity for HRAS was changed to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Mode of inheritance for HRAS was changed to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
This gene has been classified as Green List (High Evidence).
Phenotypes for gene HRAS were set to Costello syndrome;Noonan Spectrum Disorders;Noonan syndrome;Noonan syndrome plus other features;Legius syndrome;Cardio-facio-cutaneous syndrome;LEOPARD syndrome
HRAS was added to RASopathiespanel. Sources: Eligibility statement prior genetic testing,Radboud University Medical Center, Nijmegen,UKGTN
HRASAll sources for gene: HRAS were removed
HRAS was added to RASopathiespanel. Sources: Radboud University Medical Center, Nijmegen,Eligibility statement prior genetic testing,UKGTN
HRAS was added to RASopathiespanel. Source: UKGTN
HRAS was created by ellenmcdonagh
HRAS was added to RASopathiespanel. Sources: Emory Genetics Laboratory,Radboud University Medical Center, Nijmegen,UKGTN,Eligibility statement prior genetic testing