Beyond diagnostic yield, the study provides practical insights for labs evaluating GS as a new first-tier standard, including the added value of inheritance information for less-experienced teams and the types of variants GS captures that SoC often misses.
After a mean reanalysis interval of 660 days, manual review added 3 P/LP cases and 2 newly classified VUS. Talos recovered all 3 new P/LP findings and 1 of 2 VUS, while reducing review to ~3 candidate variants per case.
Concordance analysis showed that Talos captured most manually reported P/LP findings: 80.0% concordance in singleton cases and 75.2% in trio cases, rising to 82.8% when considering proband-only findings. VUS concordance was lower, as expected for a P/LP-focused workflow.