Paediatric or syndromic cardiomyopathy

Gene: NRAS

Green List (high evidence)

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

I don't know

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.

Green List (high evidence)

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

Phenotypes
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