biostudies-literatureUnknown10(8)Lois SNeurofibromin is engaged in many cellular processes and when the proper protein functioning is impaired, it causes neurofibromatosis type 1 (<i>NF1</i>), one of the most common inherited neurological disorders. Recent advances in sequencing and screening of the <i>NF1</i> gene have increased the number of detected variants. However, the correlation of these variants with the clinic remains poorly understood. In this study, we analyzed 4610 germinal <i>NF1</i> variants annotated in ClinVar and determined on exon level the mutational spectrum and potential pathogenic regions. Then, a binomial and sliding windows test using 783 benign and 938 pathogenic <i>NF1</i> variants were analyzed against functional and structural regions of neurofibromin. The distribution of synonymous, missense, and fBiomedicines2044https://www.ebi.ac.uk/biostudies/studies/S-EPMC9405573biostudies-literatureIdentification of Germinal Neurofibromin Hotspots.PMC9405573Trivino JCLacal JBaez-Flores JLois SIsidoro-Garcia MfalseIdentification of Germinal Neurofibromin Hotspots.Neurofibromin is engaged in many cellular processes and when the proper protein functioning is impaired, it causes neurofibromatosis type 1 (<i>NF1</i>), one of the most common inherited neurological disorders. Recent advances in sequencing and screening of the <i>NF1</i> gene have increased the number of detected variants. However, the correlation of these variants with the clinic remains poorly understood. In this study, we analyzed 4610 germinal <i>NF1</i> variants annotated in ClinVar and determined on exon level the mutational spectrum and potential pathogenic regions. Then, a binomial and sliding windows test using 783 benign and 938 pathogenic <i>NF1</i> variants were analyzed against functional and structural regions of neurofibromin. The distribution of synonymous, missense, and f2022-01-01T00:00:00Z2022 Aug2026-06-20T03:24:31.505Z2024-11-08T20:15:46.365ZS-EPMC94055733600959110.3390/biomedicines10082044