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Background  Laboratory assays evaluating the effect of DNA sequence variants on  BRCA1  mRNA splicing may contribute to classification by providing molecular evidence. However, our knowledge of normal and aberrant  BRCA1  splicing events to date has been limited to data derived from assays targeting partial transcript sequences. This study explored the utility of nanopore sequencing to examine whole  BRCA1  mRNA transcripts and to provide accurate categorisation of in-frame and out-of-frame splicing events.    Methods  The exon structure of  BRCA1  transcripts from a previously studied control lymphoblastoid cell line were assessed using MinION nanopore sequencing of long-range reverse transcriptase-PCR amplicons.    Results  Our study identified and characterised 32 complete  BRCA1  isoforms, including 18 novel isoforms which showed skipping of multiple contiguous and/or non-contiguous exons. Furthermore, we show that known  BRCA1  exon skipping events, such as Δ(9,10) and Δ21, can co-occur in a single transcript, with some isoforms containing four or more alternative splice junctions. Fourteen novel isoforms were formed entirely from a combination of previously identified alternative splice junctions, suggesting that the total number of  BRCA1  isoforms might be lower than the number of splicing events reported previously.    Conclusions  Our results highlight complexity in  BRCA1  transcript structure that has not been described previously. This finding has key implications for predicting the translation frame of splicing transcripts, important for interpreting the clinical significance of spliceogenic variants. Future research is warranted to quantitatively assess full-length  BRCA1  transcript levels, and to assess the application of nanopore sequencing for routine evaluation of potential spliceogenic variants.    Electronic supplementary material  The online version of this article (doi:10.1186/s13058-017-0919-1) contains supplementary material, which is available to authorized users.

Nanopore sequencing of full-length BRCA1 mRNA transcripts reveals co-occurrence of known exon skipping events