Large gene panel sequencing in clinical diagnostics-results from 501 consecutive cases

Area of Science:

• Genomics
• Clinical Diagnostics
• Molecular Biology

Background:

• Large gene panels are increasingly used for high-throughput sequencing in clinical settings.
• The clinical utility of these large gene panels remains less investigated compared to whole exome sequencing.

Purpose of the Study:

• To investigate the clinical utility of large gene panel sequencing.
• To assess the diagnostic yield of targeted gene panels versus broader panels.

Main Methods:

• Sequencing of the TruSight One panel (Illumina) in 501 unselected cases.
• Analysis focused on virtual subpanels based on clinician-specified genes or predefined larger panels.

Main Results:

• A pathogenic finding was reported in 26.3% of cases.
• Targeted analysis of 1-9 genes yielded a significantly higher diagnostic rate (31.5%) compared to larger panels (21.7%).
• Detected mutations included single nucleotide variants, insertions/deletions, and copy number variants, with 67 previously undescribed mutations.

Conclusions:

• Large gene panel sequencing demonstrates significant clinical utility.
• The diagnostic yield is influenced by the number of genes analyzed, with smaller, targeted panels showing higher efficiency.