ClinVar

Description

This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 441 of the PRKN protein (p.Cys441Arg). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects PRKN function (PMID: 16714300, 19801972, 25591737). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PRKN protein function. ClinVar contains an entry for this variant (Variation ID: 963190). This missense change has been observed in individual(s) with juvenile Parkinson's disease (PMID: 12116199, 27206984). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs778305273, gnomAD 0.06%).