ClinVar

Description

This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 209 of the BAG3 protein (p.Pro209Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Charcot-Marie-Tooth disease (PMID: 27164712, 28754666). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 657299). 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 BAG3 protein function. Experimental studies have shown that this missense change affects BAG3 function (PMID: 30559338). For these reasons, this variant has been classified as Pathogenic.