Cardiomyopathies - including childhood onsetGene: NRAS
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
Noonan syndrome 6 OMIM#613224 and somatic cancers
Created: 25 Mar 2019, 4:30 p.m.
In HGMD mainly associated with Noonans/Costello syndrome HCM or CHD cardiac anomalies. Cirstea Nat Genet. 2010 Jan;42(1):27-9.
Created: 25 Mar 2019, 4:27 p.m.
Comment on mode of pathogenicity: Gain of function variants suggested by reviewer, and G2P indicates activating consequence of mutations. Comments from Reviewer: Gain of functions mutations in NRAS are a rare cause of Noonan syndrome and may also be associated with CFC. To date, two mutations have been reported to cause Noonan syndrome: p.Thr50Ile; p.Gly60Glu. - Helen Savage (Congenica Ltd), Jan. 21, 2016, 11:01 a.m. Gain of function mutations in NRAS cause Noonan syndrome and Cardio-Facio-cutanenous syndrome. This disorders share phenotypes with Legius syndrome. No reports of mutations in NRAS causing Legius syndrome. - Helen Savage (Congenica Ltd), Jan. 25, 2016, 11:44 a.m. Two gain of functions mutations in NRAS (p.Thr50Ile; p.Gly60Glu) reported to cause Noonan syndrome. - Helen Savage (Congenica Ltd), Jan. 21, 2016, 2:06 p.m.
Created: 5 Feb 2016, 12:31 p.m.
Comment on mode of inheritance: Monoallelic confirmed on G2P, and not on imprinted gene list.
Created: 4 Feb 2016, 5:12 p.m.
Gain of function mutations. 2 common mutations p.Thr50Ile; p.Gly60Glu
Created: 1 Feb 2016, 10:48 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cardio-Facio-cutanenous syndrome; Noonan syndrome
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 NRAS.
Source Expert List was added to NRAS. Mode of pathogenicity for gene NRAS 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 CFC Syndrome; Cardio-Facio-cutanenous syndrome; Noonan syndrome 6 613224 for gene: NRAS Publications for gene NRAS were changed from 19775298; PMID: 19966803 to 19775298; 19966803
gene: NRAS was added gene: NRAS was added to Cardiomyopathies - including childhood onset. Sources: Expert Review Green,London South GLH,South West GLH Mode of inheritance for gene: NRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NRAS were set to 19775298; PMID: 19966803 Phenotypes for gene: NRAS were set to CFC Syndrome; Noonan syndrome; syndromic HCM; Noonan syndrome 6; Cardio-Facio-cutanenous syndrome