Clinical genetics and the problem of uncertain significance
10 days ago
- #clinical genetics
- #genetic testing
- #VUS
- Genetic testing often results in variants of unknown significance (VUS), creating uncertainty for patients.
- VUS arise due to the gap between detecting genetic variants and understanding their biological impact.
- More data, family studies, and functional evidence can help reclassify VUS, but challenges remain.
- Multiplexed Assays of Variant Effect (MAVEs) offer a promising approach to generate functional data on a large scale.
- MAVE data can improve pathogenicity predictors and aid in VUS reclassification.
- Despite progress, only a fraction of the genome has been comprehensively assessed, highlighting the need for more research.
- 20%-40% of patients undergoing genetic testing receive a VUS, underscoring the prevalence of this issue.
- The NHGRI aims to solve the VUS problem by 2030, with MAVE data playing a crucial role.