There was only sufficient evidence in the literature for the association between RAF1 and Noonan syndrome with multiple lentigines (NSML) association to be classified as Limited. Only two variants with supporting evidence for pathogenicity (one de novo) in this gene have been found in individuals with NSML (Carcavilla et al., 2013; Kuburovic, Vukomanovic, Carcavilla, Ezquieta-Zubicaray, & Kuburovic, 2011; Pandit et al., 2007). The RAF1 gene is also located in the Ras/MAPK pathway, which is associated with the NSML phenotype (Aoki et al., 2016; Rauen, 2013). Of note, RAF1 is also classified as Definitive in association with Noonan syndrome (NS) and as Disputed in association with Costello syndrome and cardiofaciocutaneous syndrome. The ClinGen RASopathy Expert Panel found no evidence associating RAF1 with NS-like disorder with loose anagen hair. This curation was approved by the ClinGen RASopathy Gene Curation Expert Panel on 7/25/18 (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).
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. The GenCC does not independently verify the submitted information. Though the information is obtained from sources believed to be reliable, no warranty, expressed or implied, is made regarding accuracy, adequacy, completeness, reliability or usefulness of any information. This disclaimer applies to both isolated and aggregate uses of the information. The information is provided on an "as is" basis, collected through periodic submission and therefore may not represent the most up-to-date information from the submitters. If you have questions about the medical relevance of information contained on this website, please see a healthcare professional; if you have questions about specific gene-disease claims, please contact the relevant sources; and if you have questions about the representation of the data on this website, please contact gencc@thegencc.org.