New insights into the pathogenicity of non-synonymous variants through multi-level analysis.

ABSTRACT: Precise classification of non-synonymous single nucleotide variants (SNVs) is a fundamental goal of clinical genetics. Next-generation sequencing technology is effective for establishing the basis of genetic diseases. However, identification of variants that are causal for genetic diseases remains a challenge. We analyzed human non-synonymous SNVs from a multilevel perspective to characterize pathogenicity. We showed that computational tools, though each having its own strength and weakness, tend to be overly dependent on the degree of conservation. For the mutations at non-degenerate sites, the amino acid sites of pathogenic substitutions show a distinct distribution in the classes of protein domains compared with the sites of benign substitutions. Overlooked disease susceptibility of gen

SUBMITTER: Sun H 

PROVIDER: S-EPMC6367327 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature