There is a definitive association between alteration of the RIT1 gene and the Noonan syndrome (NS) phenotype. The maximum amount of scorable genetic evidence has been published showing de novo as well as segregating variants occur in RIT1 in patients with NS (Aoki et al., 2013; Bertola et al., 2014; Chen et al., 2014; Koenighofer et al., 2016; Kouz et al., 2016). The RIT1 gene is also located in the Ras/MAPK pathway which is associated with the NS phenotype and RIT1 variants found in NS patients disrupt the RAS pathway function as demonstrated by zebrafish models (Aoki et al., 2013; Aoki et al., 2016; Koenighofer et al., 2016; Rauen, 2013). The ClinGen RASopathy Expert Panel found no evidence associating RIT1 with cardiofaciocutaneous syndrome, Costello syndrome, NS with loose anagen hair or NS with multiple lentigines. This curation was approved by the ClinGen RASopathy Gene Curation Expert Panel on 7/24/18 (SOP Version 5).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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