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Through target enrichment of the transcriptome, it is possible to perform deep\u2010sequencing and to identify the different and even rare mRNA isoforms. A targeted RNA\u2010seq approach was used to analyse the naturally\u2010occurring splicing events for a panel of 8 breast and\/or ovarian cancer susceptibility genes (<jats:italic>BRCA1<\/jats:italic>, <jats:italic>BRCA2<\/jats:italic>, <jats:italic>RAD51C<\/jats:italic>, <jats:italic>RAD51D<\/jats:italic>, <jats:italic>PTEN<\/jats:italic>, <jats:italic>STK11<\/jats:italic>, <jats:italic>CDH1<\/jats:italic>, <jats:italic>TP53<\/jats:italic>), 3 Lynch syndrome genes (<jats:italic>MLH1, MSH2<\/jats:italic>, <jats:italic>MSH6<\/jats:italic>) and the fanconi anaemia <jats:italic>SLX4<\/jats:italic> gene, in which monoallelic mutations were found in non\u2010<jats:italic>BRCA<\/jats:italic> families. For <jats:italic>BRCA1<\/jats:italic>, <jats:italic>BRCA2<\/jats:italic>, <jats:italic>RAD51C<\/jats:italic> and <jats:italic>RAD51D<\/jats:italic> the results were validated by capillary electrophoresis and were compared to a non\u2010targeted RNA\u2010seq approach. We also compared splicing events from lymphoblastoid cell\u2010lines with those from breast and ovarian fimbriae tissues. The potential of targeted RNA\u2010seq to detect pathogenic changes in RNA\u2010splicing was validated by the inclusion of samples with previously well characterized <jats:italic>BRCA1\/2<\/jats:italic> genetic variants. In our study, we update the catalogue of normal splicing events for <jats:italic>BRCA1\/2,<\/jats:italic> provide an extensive catalogue of normal <jats:italic>RAD51C<\/jats:italic> and <jats:italic>RAD51D<\/jats:italic> alternative splicing, and list splicing events found for eight other genes. Additionally, we show that our approach allowed the identification of aberrant splicing events due to the presence of <jats:italic>BRCA1<\/jats:italic>\/<jats:italic>2<\/jats:italic> genetic variants and distinguished between complete and partial splicing events. In conclusion, targeted\u2010RNA\u2010seq can be very useful to classify variants based on their putative pathogenic impact on splicing.<\/jats:p>","DOI":"10.1002\/ijc.32114","type":"journal-article","created":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T07:46:22Z","timestamp":1547019982000},"page":"401-414","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Targeted RNA\u2010seq successfully identifies normal and pathogenic splicing events in breast\/ovarian cancer susceptibility and Lynch syndrome genes"],"prefix":"10.1002","volume":"145","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7597-5764","authenticated-orcid":false,"given":"Rita D.","family":"Brand\u00e3o","sequence":"first","affiliation":[{"name":"Department of Clinical Genetics Maastricht University Medical Centre+, GROW\u2010 School for Oncology and Developmental Biology  Maastricht The 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