ClinVar

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Arg1391 amino acid residue in NF1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7581973, 9003501, 16513807, 22807134, 27322474). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NF1 protein function. ClinVar contains an entry for this variant (Variation ID: 523345). This missense change has been observed in individual(s) with NF1- Noonan syndrome and neurofibormatosis type 1 (NF1) (PMID: 24789688, 27322474; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 1391 of the NF1 protein (p.Arg1391Thr).