Cardiomyopathies - including childhood onsetGene: MRAS
Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is also Green on the RASopathies panel (v 1.61).
Review copied from RASopathies panel:
"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.
Arina Puzriakova (Genomics England Curator), 4 Aug 2020"
Therefore, this gene will be promoted to Green status at the next major review.
Created: 8 Sep 2020, 10:40 a.m. | Last Modified: 8 Sep 2020, 10:40 a.m.
Panel Version: 1.7
At least 6 unrelated individuals reported with NS, cardiomyopathy specifically reported.
Sources: Expert list
Created: 7 Aug 2020, 1:14 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Noonan syndrome, MIM#618499
Mode of pathogenicity
Variants in this GENE are reported as part of current diagnostic practice
Phenotypes for gene: MRAS were changed from Noonan syndrome, 618499 to Noonan syndrome 11, OMIM:618499; Noonan syndrome 11, MONDO:0032786
Gene: mras has been classified as Amber List (Moderate Evidence).
Tag for-review tag was added to gene: MRAS.
Phenotypes for gene: MRAS were changed from Noonan syndrome, MIM#618499 to Noonan syndrome, 618499
gene: MRAS was added gene: MRAS was added to Cardiomyopathies - including childhood onset. 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; 31173466; 31108500; 31173466 Phenotypes for gene: MRAS were set to Noonan syndrome, MIM#618499 Mode of pathogenicity for gene: MRAS was set to Other Review for gene: MRAS was set to GREEN gene: MRAS was marked as current diagnostic