There will always be variants of uncertain significance. Analysis of VUSs.

ABSTRACT: The ACMG/AMP guidelines include five categories of which variants of uncertain significance (VUSs) have received increasing attention. Recently, Fowler and Rehm claimed that all or most VUSs could be reclassified as pathogenic or benign within few years. To test this claim, we collected validated benign, pathogenic, VUS and conflicting variants from ClinVar and LOVD and investigated differences at gene, protein, structure, and variant levels. The gene and protein features included inheritance patterns, actionability, functional categories for housekeeping, essential, complete knockout, lethality and haploinsufficient proteins, Gene Ontology annotations, and protein network properties. Structural properties included the location at secondary structural elements, intrinsically disordered reg

SUBMITTER: Zhang H 

PROVIDER: S-EPMC11616676 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature