There have been cases described in the literature with the p.Ser2Gly variant in SHOC2 who were diagnosed with Noonan syndrome (NS) but were not phenotyped for loose anagen hair (LAH) (Hoban, Roberts, Demmer, Jethva, & Shephard, 2012; Justino et al., 2015; Komatsuzaki et al., 2010). There has only been one NS case where LAH was assessed but not noted, and this individual had sparse and curly hair. Therefore, the NS/LAH phenotype cannot be ruled out for any of these patients. The p.Ser2Gly variant has been a recurrently identified variant in cases with NS/LAH, and no other variants have been identified in these patients (Cordeddu et al., 2009; Ekvall et al., 2011; Komatsuzaki et al., 2010). In summary, this association is Disputed. Of note, SHOC2 is classified as Definitive in association with NS-like disorder with loose anagen hair and as Disputed in association with Costello syndrome and cardiofaciocutaneous 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 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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