There is a definitive association between alteration of the SOS1 gene and the Noonan syndrome (NS) phenotype. The maximum amount of scorable genetic evidence has been published showing that de novo and segregating variants occur in patients with NS (Lepri et al., 2011; Louati et al., 2014; Moncini et al., 2015; Narumi et al., 2007; Roberts et al., 2007; Tartaglia et al., 2007). The SOS1 gene is also located in the Ras/MAPK pathway which is associated with the NS phenotype(Aoki et al., 2016; Rauen, 2013). Of note, SOS1 has also been classified as disputed in association with cardiofaciocutaneous syndrome and Costello syndrome. The ClinGen RASopathy Gene Curation Expert Panel found no evidence associating SOS1 with either NS with loose anagen hair or NS with multiple lentigines. This curation was approved by the ClinGen RASopathy GCEP 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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