Bridging the Functional Gap by Synergy of Exome/Genome and RNA Sequencing: A Systematic Semi-quantitative Review Demonstrating Enhanced Diagnostic Yield in Genetic Diagnostics.

Addition of RNA sequencing to WES/WGS to confirm, reclassify or discover variants

This semi-quantitative systematic review (200 studies, 2014-2024) assesses the added value of RNA sequencing alongside WES/WGS. The weighted-average diagnostic rate for WES/WGS followed by RNA-seq was 0.44 versus 0.37 for WES/WGS alone, with a trend toward improvement (OR 1.31). In patients undiagnosed by WES/WGS, RNA-seq contributed 5.4% of diagnoses via confirmation or reclassification and 3.3% via novel-variant discovery. Tissue samples outperformed blood for RNA-seq yield.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A useful synthesis quantifying the modest but real incremental value of the transcriptome complementing WES/WGS, especially for resolving candidate variants and splicing effects. Tissue choice appears decisive, with practical access implications. RNA-seq stands out as a reasoned second tier rather than a systematic test.

Analysis by Dr Thibaut Benquey