There have been 2 published cases that were initially diagnosed with suspected Costello syndrome (Komatsuzaki et al., 2010) and the p.S2G variant. However, these individuals also presented with hair anomalies consistent with loose anagen hair, therefore it was concluded both in the paper and by the RASopathy Expert Panel that these cases are more consistent with Noonan-like syndrome with loose anagen hair (NS/LAH). The p.S2G variant has been recurrently identified in cases with NS/LAH (Cordeddu et al., 2009; Ekvall, Hagenas, Allanson, Anneren, & Bondeson, 2011; Komatsuzaki et al., 2010). This association is Disputed. The HRAS gene is believed to be the only gene associated with CS (Aoki et al., 2005; Estep, Tidyman, Teitell, Cotter, & Rauen, 2006; Gripp et al., 2006; Kerr et al., 2006; Zampino et al., 2007). Of note, SHOC2 is classified as Definitive in association with NS/LAH and as Disputed in association with NS 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 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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