RASopathies

Gene: HRAS

Green List (high evidence)

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

• https://doi.org/10.1038/s41431-020-0662-4

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.

Green List (high evidence)

Gain of function mutations

Created: 1 Feb 2016, 10:44 a.m.

Gain of function mutations

Created: 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