Diana Eccles|Gillian Mitchell|Alvaro N.A. Monteiro|Rita K. Schmutzler|Fergus J. Couch|Amanda B. Spurdle|Encarna B. Gómez-García|Rebecca Driessen|Noralane M. Lindor|Marinus J. Blok|Per W. Möller|Miguel de la Hoya|Tuya Pal|S. M. Domchek|Katherine L. Nathanson|Christi J. van Asperen|Orland D??ez|K. Rheim|Dominique Stoppa?Lyonnet|Michael T. Parsons|David E. Goldgar
BRCA1 and BRCA2 genetic testing—pitfalls and recommendations for managing variants of uncertain clinical significance
Southampton General Hospital|University of British Columbia|Peter MacCallum Cancer Centre|University of Melbourne|Moffitt Cancer Center|University Hospital Cologne|Mayo Clinic|QIMR Berghofer Medical Research Institute|Maastricht University Medical Centre|University Hospital Cologne|QIMR Berghofer Medical Research Institute|QIMR Berghofer Medical Research Institute|QIMR Berghofer Medical Research Institute
increasing use brca12 testing tailoring cancer treatment extension testing tumour tissue somatic mutation moving brca12 mutation screening primarily prevention arena delivered specialist genetic services mainstream oncology practice considerable number gene tests identify rare variants clinical significance cannot inferred sequence information alone proportion variants uncertain clinical significance vus likely grow lower thresholds testing laboratory providers less experience brca vus associated high risk cancer misinterpreted vus potential lead mismanagement patient relativesmembers clinical working group enigma evidencebased network interpretation germline mutant alleles global consortium wwwenigmaconsortiumorg observed wide variation practices reporting disclosure clinical management patients vus examples current clinical practice presented discussed illustrate potential pitfalls explore factors contributing misinterpretation propose approaches improving clarityclinicians patients relatives would benefit improved level genetic literacy genetic laboratories working clinical geneticists need agree clinically clear uniform format reporting brca test results nongeneticists international consortium experts collecting integrating available lines evidence classifying variants according internationally recognized system facilitate reclassification variants clinical use