RASopathies
Gene: MRAS
Associated with Noonan syndrome in OMIM and G2P (confirmed).
PMID: 28289718 (2017) - In two unrelated patients with Noonan syndrome and cardiac hypertrophy, trio WES/targeted sequencing revealed de novo missense variants (c.68G>T, p.G23V and c.203C>T, p.T68I) in the MRAS gene. Functional studies of the p.Gly23Val variant showed the change yields a constitutively active form of MRAS.
PMID: 31173466 (2019) - One patient with a severe a Noonan syndrome phenotype, associated with a de novo MRAS variant (c.212A>G, p.Q71R). Functional studies were not performed.
PMID: 31108500 (2020) - Two unrelated patients with Noonan syndrome, including hypertrophic cardiomyopathy and dysmorphic features. Targeted sequencing revealed de novo activating MRAS variants (c.203C>T, p.T68I and c.67G>C, p.G23R). Functional studies demonstrated that the variants yields a constitutively active form of MRAS.Created: 4 Aug 2020, 4:05 p.m. | Last Modified: 4 Aug 2020, 4:06 p.m.
Panel Version: 1.55
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Noonan syndrome 11, 618499
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Two unrelated individuals reported with de novo variants in this gene initially. Rated as LIMITED by ClinGen in 2018. Note 4 further individuals reported since.
Sources: Expert listCreated: 3 Jul 2020, 10:34 a.m. | Last Modified: 3 Jul 2020, 10:39 a.m.
Panel Version: 1.55
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Noonan syndrome
Publications
Phenotypes for gene: MRAS were changed from Noonan syndrome 11, 618499 to Noonan syndrome 11, OMIM:618499; Noonan syndrome 11, MONDO:0032786
Publications for gene: MRAS were set to 28289718
Phenotypes for gene: MRAS were changed from Noonan syndrome to Noonan syndrome 11, 618499
Gene: mras has been classified as Green List (High Evidence).
gene: MRAS was added gene: MRAS was added to RASopathies. Sources: Expert list Mode of inheritance for gene: MRAS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MRAS were set to 28289718 Phenotypes for gene: MRAS were set to Noonan syndrome Review for gene: MRAS was set to AMBER