Inferring the molecular and phenotypic impact of amino acid variants with MutPred2.

ABSTRACT: Identifying pathogenic variants and underlying functional alterations is challenging. To this end, we introduce MutPred2, a tool that improves the prioritization of pathogenic amino acid substitutions over existing methods, generates molecular mechanisms potentially causative of disease, and returns interpretable pathogenicity score distributions on individual genomes. Whilst its prioritization performance is state-of-the-art, a distinguishing feature of MutPred2 is the probabilistic modeling of variant impact on specific aspects of protein structure and function that can serve to guide experimental studies of phenotype-altering variants. We demonstrate the utility of MutPred2 in the identification of the structural and functional mutational signatures relevant to Mendelian disorders and t

SUBMITTER: Pejaver V 

PROVIDER: S-EPMC7680112 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature