PT - JOURNAL ARTICLE AU - Amanda B Spurdle AU - Stephanie Greville-Heygate AU - Antonis C Antoniou AU - Melissa Brown AU - Leslie Burke AU - Miguel de la Hoya AU - Susan Domchek AU - Thilo Dörk AU - Helen V Firth AU - Alvaro N Monteiro AU - Arjen Mensenkamp AU - Michael T Parsons AU - Paolo Radice AU - Mark Robson AU - Marc Tischkowitz AU - Emma Tudini AU - Clare Turnbull AU - Maaike PG Vreeswijk AU - Logan C Walker AU - Sean Tavtigian AU - Diana M Eccles TI - Towards controlled terminology for reporting germline cancer susceptibility variants: an ENIGMA report AID - 10.1136/jmedgenet-2018-105872 DP - 2019 Jun 01 TA - Journal of Medical Genetics PG - 347--357 VI - 56 IP - 6 4099 - http://jmg.bmj.com/content/56/6/347.short 4100 - http://jmg.bmj.com/content/56/6/347.full SO - J Med Genet2019 Jun 01; 56 AB - 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The language used to describe variants identified in cancer susceptibility genetic testing typically still reflects an outdated paradigm of Mendelian inheritance with dichotomous outcomes.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.