ClinVar

Description

This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 117 of the NPC1 protein (p.Gln117Arg). ClinVar contains an entry for this variant (Variation ID: 581349). This missense change has been observed in individual(s) with Niemann-Pick disease type C (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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 NPC1 protein function.