Can Predicted Protein 3D Structures Provide Reliable Insights into whether Missense Variants Are Disease Associated?

ABSTRACT: Knowledge of protein structure can be used to predict the phenotypic consequence of a missense variant. Since structural coverage of the human proteome can be roughly tripled to over 50% of the residues if homology-predicted structures are included in addition to experimentally determined coordinates, it is important to assess the reliability of using predicted models when analyzing missense variants. Accordingly, we assess whether a missense variant is structurally damaging by using experimental and predicted structures. We considered 606 experimental structures and show that 40% of the 1965 disease-associated missense variants analyzed have a structurally damaging change in the mutant structure. Only 11% of the 2134 neutral variants are structurally damaging. Importantly, similar results

SUBMITTER: Ittisoponpisan S 

PROVIDER: S-EPMC6544567 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature