Patient assessment and selection of variants for testing
The Erasmus MC Department of Clinical Genetics NF1/LS cohort consists of >4900 index cases suspected of NF1 or LS based on the international clinical diagnostic criteria [Legius et al., 2021] for whom DNA has been submitted for genetic testing of NF1 and/orSPRED1 . Prior to functional testing, variants were classified using the available clinical and genetic data. Nomenclature for all the reported variants is according to HGVS guidelines [HGVS, 2016]. For assay validation, we included 8 variants that had been classified as pathogenic and/or subjected to functional evaluation previously: NF1 p.Leu90Pro [Xiao et al., 2018], p.Met992del [Koczkowska et al., 2020], p.Asp1217Tyr [Hirata et al., 2016], p.Arg1276Gly [Mattocks et al., 2004] and p.Lys1423Glu [Thomas et al., 2012, Koczkowska et al., 2019]; and SPRED1 p.Val44Asp, p.Thr102Met [Hirata et al., 2016] and p.Ser105Ala [Yan et al., 2020].