Missense variants pathogenicity annotation from homologous proteins.

ABSTRACT:

Motivation

High-throughput DNA sequencing has revealed millions of single nucleotide variants (SNVs) in the human genome, with a small fraction linked to disease. The effect of missense variants, which alter the protein sequence, is particularly challenging to interpret due to the scarcity of clinical annotations and experimental information. While using conservation and structural information, current prediction tools still struggle to predict variant pathogenicity. In this study, we explored the pathogenicity of homologous missense variants-variants in equivalent positions across homologous proteins-focusing on proteins involved in autosomal dominant diseases.

Results

Our analysis of 2976 pathogenic and 17 555 non-pathogenic homologous variants demonstrated that pathogenic

SUBMITTER: Ruiz-Alias G 

PROVIDER: S-EPMC12122210 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature