Predicting the pathogenicity of missense variants based on protein instability to support diagnosis of patients with novel variants of ARSL.

ABSTRACT: Rare diseases are estimated to affect 3.5%-5.9% of the population worldwide and are difficult to diagnose. Genome analysis is useful for diagnosis. However, since some variants, especially missense variants, are also difficult to interpret, tools to accurately predict the effect of missense variants are very important and needed. Here we developed a method, "VarMeter", to predict whether a missense variant is damaging based on Gibbs free energy and solvent-accessible surface area calculated from the AlphaFold 3D protein model. We applied this method to the whole-exome sequencing data of 900 individuals with rare or undiagnosed disease in our in-house database, and identified four who were hemizygous for missense variants of arylsulfatase L (ARSL; known as the genetic cause of chondrodyspla

SUBMITTER: Aoki E 

PROVIDER: S-EPMC10694752 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature