Towards controlled terminology for reporting germline cancer susceptibility variants: An ENIGMA report

Amanda B. Spurdle, Stephanie Greville-Heygate, Antonis C. Antoniou, Melissa Brown, Leslie Burke, Miguel De La Hoya, Susan Domchek, Thilo Dörk, Helen V. Firth, Alvaro N. Monteiro, Arjen Mensenkamp, Michael T. Parsons, Paolo Radice, Mark Robson, Marc Tischkowitz, Emma Tudini, Clare Turnbull, Maaike P.G. Vreeswijk, Logan C. Walker, Sean TavtigianDiana M. Eccles

Research output: Contribution to journalArticlepeer-review


The vocabulary currently used to describe genetic variants and their consequences reflects many years of studying and discovering monogenic disease with high penetrance. With the recent rapid expansion of genetic testing brought about by wide availability of high-throughput massively parallel sequencing platforms, accurate variant interpretation has become a major issue. The vocabulary used to describe single genetic variants in silico, in vitro, in vivo and as a contributor to human disease uses terms in common, but the meaning is not necessarily shared across all these contexts. In the setting of cancer genetic tests, the added dimension of using data from genetic sequencing of tumour DNA to direct treatment is an additional source of confusion to those who are not experienced in cancer genetics. The language used to describe variants identified in cancer susceptibility genetic testing typically still reflects an outdated paradigm of Mendelian inheritance with dichotomous outcomes. Cancer is a common disease with complex genetic architecture; an improved lexicon is required to better communicate among scientists, clinicians and patients, the risks and implications of genetic variants detected. This review arises from a recognition of, and discussion about, inconsistencies in vocabulary usage by members of the ENIGMA international multidisciplinary consortium focused on variant classification in breast-ovarian cancer susceptibility genes. It sets out the vocabulary commonly used in genetic variant interpretation and reporting, and suggests a framework for a common vocabulary that may facilitate understanding and clarity in clinical reporting of germline genetic tests for cancer susceptibility.

Original languageEnglish
JournalJournal of Medical Genetics
Publication statusAccepted/In press - Jan 1 2019


  • cancer susceptibility
  • genetic variant
  • interpretation
  • reporting
  • vocabulary

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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