Cardiomyopathies - including childhood onsetGene: HRAS
Submitted on behalf of the GMS Cardiology specialist group. The group has agreed that this gene should be Green on this panel.
Created: 2 Dec 2019, 3:58 p.m. | Last Modified: 2 Dec 2019, 3:58 p.m.
Panel Version: 0.16
OMIM: https://omim.org/clinicalSynopsis/218040 - lists HCM and other anomalies such as CHD features. HGMD: mainly costello syndrome 1 report of HCM on it's own. : Sana (2016) A Novel HRAS Mutation Independently Contributes to Left Ventricular Hypertrophy in a Family with a Known MYH7 Mutation. PLoS ONE 1(12): e0168501.doi:10.1371/journal.pone.0168501: HRAS variant detected in an affected adult with HCM who did not have a known familial MYH7 variant his daughter also carried the variants who had HCM and intellectual disability - no paediatric onset.
Created: 25 Mar 2019, 4:27 p.m.
Variants in this GENE are reported as part of current diagnostic practice
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 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
Source NHS GMS was added to HRAS.
Source Expert List was added to HRAS. Mode of pathogenicity for gene HRAS was changed from to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Added phenotypes Costello syndrome for gene: HRAS Publications for gene HRAS were changed from PMID: 16170316; 21396583; 16969868; 16443854 to 16170316; 16443854; 21396583; 16969868
gene: HRAS was added gene: HRAS was added to Cardiomyopathies - including childhood onset. Sources: Expert Review Green,London South GLH,South West GLH Mode of inheritance for gene: HRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: HRAS were set to PMID: 16170316; 21396583; 16969868; 16443854 Phenotypes for gene: HRAS were set to Costello syndrome; syndromic HCM