There is a definitive association between alteration of the BRAF gene and cardiofaciocutaneous (CFC) syndrome. The maximum amount of scorable genetic evidence has been published showing de novo as well as non-de novo variants occur in BRAF in patients with CFC syndrome (Gripp et al., 2007; Louati et al., 2014; Makita et al., 2007; Mucciolo, Dello Russo, D'Emidio, Mesoraca, & Giorlandino, 2016; Narumi et al., 2007; Niihori et al., 2006; Rodriguez-Viciana, Tetsu, et al., 2006). The BRAF gene is located in the Ras/MAPK pathway which is associated with the Noonan phenotype and variants found in CFC patients in this gene disrupt the RAS pathway function as demonstrated by both mouse and zebrafish models (Anastasaki, Estep, Marais, Rauen, & Patton, 2009; Aoki et al., 2016; Moriya et al., 2015; Rauen, 2013). Of note, BRAF has also been classified as moderate in association with Noonan syndrome (NS), limited in association with NS with multiple lentigines, and disputed in association with Costello syndrome. The ClinGen RASopathy Expert Panel found no evidence associating BRAF with NS with loose anagen hair. 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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