Cardiomyopathies - including childhood onsetGene: KRAS
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
Cardiofaciocutaneous syndrome 2 OMIM#615278; Noonan syndrome 3 OMIM#609942 AD 3 RAS-associated autoimmune leukoproliferative disorder OMIM#614470 includes also a number of somatic cancers.
Created: 25 Mar 2019, 4:30 p.m.
Not listed with cardiomyopathies. Through OMIM clinical synopsis - HCM occurs but many other cardiac features including CHD. Not a major feature . HGMD has many phenotypes associated including a variety of cancers. Rasopathy gene - childhood onset and denovo variants reported Stark Clin Genet. 2012 Jun;81(6):590-4.
Created: 25 Mar 2019, 4:27 p.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Variants in this GENE are reported as part of current diagnostic practice
Comment on mode of pathogenicity: Actvating mutation consequence from G2P. Comments from Reviewer: <5% of cases of CFC are caused by activating mutations in KRAS. activating mutations in the gene are also known to cause <5% of cases of Noonan syndrome. - Helen Savage (Congenica Ltd), Jan. 21, 2016, 10:28 a.m. Gain of function mutations in KRAS cause Noonan syndrome and Cardio-Facio-cutanenous syndrome. This disorders share phenotypes with Legius syndrome. No reports of mutations in KRAS causing Legius syndrome. - Helen Savage (Congenica Ltd), Jan. 25, 2016, 11:43 a.m. Gain of function mutations in KRAS are found in up to 5% of patients with Noonan syndrome and up to 5% of patients with CFC. - Helen Savage (Congenica Ltd), Jan. 21, 2016, 1:26 p.m.
Created: 5 Feb 2016, 12:14 p.m.
Comment on mode of inheritance: Monoallelic confirmed in G2P, and not on imprinted gene list.
Created: 4 Feb 2016, 3:56 p.m.
Gain of function mutations
Created: 1 Feb 2016, 10:43 a.m.
Noonan syndrome; Cardio-Facio-cutanenous 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 KRAS.
Source Expert List was added to KRAS. Mode of pathogenicity for gene KRAS 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 Cardiofaciocutaneous syndrome 2 615278; Noonan syndrome 3 609942 for gene: KRAS
gene: KRAS was added gene: KRAS was added to Cardiomyopathies - including childhood onset. Sources: Expert Review Green,London South GLH,South West GLH Mode of inheritance for gene: KRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KRAS were set to PMID: 21396583 Phenotypes for gene: KRAS were set to Noonan syndrome; Cardio-Facio-Cutaneous syndrome; CFC syndrome; Cardiofaciocutaneous syndrome 2; Cardiofaciocutaneous Syndrome; Noonan syndrome 3