RNA splicing evidence enables robust classification of BRCA1 exon 18 variants: Results from the ENIGMA consortium

Using RNA and mESC functional analyses of 166 BRCA1 exon 18 variants, this ENIGMA study defines evidence-based thresholds for interpreting variants that induce skipping of this in-frame exon. The findings demonstrate that exon 18 skipping is poorly tolerated and that RNA evidence substantially improves variant classification and reduces diagnostic uncertainty.