Summary
Background: Traditional phenotype-first exome analysis can miss clinically relevant variants when clinical information is limited, atypical, or when gene–phenotype relationships are incomplete. This study evaluated the efficiency of a genotype-first strategy, prioritizing variant properties (frequency, predicted protein effect, inheritance) before phenotype.
Methods: Retrospective review of 731 whole exome sequencing cases analyzed using a genotype-first approach.
Key findings: The overall diagnostic yield was 37%. Additionally, candidate variants were reported in 19% of patients.
Conclusions: A genotype-first approach is an effective analysis strategy, identifying both definitive variants in known disease genes and strong candidates in novel genes, enabling more proactive patient management and family counseling.
Authors:
Kirsty Wells, Lotta Koskinen, Raquel Perez-Carro, Sari Tuupanen, Tiia Kangas-Kontio