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].