There has only been one case identified with suspected cardiofaciocutaneous syndrome (CFC) and a RAF1 variant (Hakami, Dillon, Lebo, & Mason-Suares, 2016). The patient was a newborn and the CFC diagnosis was based on prenatal findings of cystic hygroma, congenital heart defect and increased nuchal translucency combined with newborn phenotyping. The study admits that the diagnosis for a specific Noonan spectrum disorder may be inaccurate, as facial anomalies change with time. The p.S257L variant has also been identified in cases with RAF1-Noonan syndrome (NS). Therefore, this association is classified as Disputed. Of note, RAF1 is also classified as Definitive in association with Noonan syndrome (NS), Limited in association with NS with multiple lentigines, and as Disputed in association with Costello 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 5/31/18 (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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