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RNA sequencing uncovers clinically actionable germline intronic MSH2 variants in previously unresolved Lynch syndrome families
  1. Kelly Fulk1,
  2. Morgan Turner2,
  3. Amanda Eppolito3 and
  4. Rebekah Krukenberg4
  1. 1Ambry Genetics Corp, Aliso Viejo, California, USA
  2. 2Inova Primary Care, Falls Church, Virginia, USA
  3. 3Piedmont Healthcare Inc, Atlanta, Georgia, USA
  4. 4Community Health Network Inc, Indianapolis, Indiana, USA
  1. Correspondence to Kelly Fulk; kfulk{at}


Despite advances in genetic testing for Lynch syndrome, nearly one quarter of mismatch repair-deficient (MMRd) colorectal and endometrial cancers remain unexplained. When added to germline DNA testing, RNA sequencing can increase diagnostic yield, improve variant classification and reduce variants of uncertain significance. Here, we describe two cases where RNA sequencing uncovered likely pathogenic MSH2 variants in families with MMRd tumours that were initially unexplained following comprehensive genetic testing for Lynch syndrome.

  • Genetic screening / counselling
  • Oncology

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  • Contributors KF wrote the manuscript. MT, AE and RK saw patients described in this case report and contributed to the editing process.

  • Funding This study was funded by Ambry Genetics (N/A).

  • Case reports provide a valuable learning resource for the scientific community and can indicate areas of interest for future research. They should not be used in isolation to guide treatment choices or public health policy.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.