There is a definitive association between alteration of the SHOC2 gene and Noonan syndrome with loose anagen hair (NS/LAH). The maximum amount of scorable genetic evidence has been published showing the de novo p.Ser2Gly variant occurs in SHOC2 in patients with NS/LAH (Cordeddu et al., 2009; Galperin, Abdelmoti, & Sorkin, 2012; Motta et al., 2016). Additionally, the p.Met173Ile variant has been identified in one family with disease (Hannig, Jeoung, Jang, Phillips, & Galperin, 2014). The SHOC2 gene is also associated with the Ras/MAPK pathway, which is associated with the NS/LAH phenotype and variants found in NS/LAH patients in this gene disrupt the RAS pathway function as demonstrated by C. elegans models (Cordeddu et al., 2009; Gripp et al., 2016). Of note, SHOC2 is also classified as Disputed in association with NS, cardiofaciocutaneous syndrome, and Costello syndrome. The ClinGen RASopathy Expert Panel found no evidence associating SHOC2 with NS with multiple lentigines. 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).
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