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Original article
BRCA1 Circos: a visualisation resource for functional analysis of missense variants
  1. Ankita Jhuraney1,2,
  2. Aneliya Velkova1,24,
  3. Randall C Johnson3,
  4. Bailey Kessing3,
  5. Renato S Carvalho4,5,
  6. Phillip Whiley6,
  7. Amanda B Spurdle6,
  8. Maaike P G Vreeswijk7,
  9. Sandrine M Caputo8,
  10. Gael A Millot9,
  11. Ana Vega10,
  12. Nicolas Coquelle11,
  13. Alvaro Galli12,
  14. Diana Eccles13,
  15. Marinus J Blok14,
  16. Tuya Pal1,
  17. Rob B van der Luijt15,
  18. Marta Santamariña Pena16,
  19. Susan L Neuhausen17,
  20. Talia Donenberg18,
  21. Eva Machackova19,
  22. Simon Thomas20,
  23. Maxime Vallée21,
  24. Fergus J Couch22,
  25. Sean V Tavtigian23,
  26. J N Mark Glover11,
  27. Marcelo A Carvalho4,5,
  28. Lawrence C Brody24,
  29. Shyam K Sharan25,
  30. Alvaro N Monteiro1,
  31. on behalf of the ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) Consortium
  1. 1Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA
  2. 2University of South Florida Cancer Biology PhD Program, Tampa, Florida, USA
  3. 3Frederick National Laboratory for Cancer Research, National Cancer Institute, Fredrick, Maryland, USA
  4. 4Instituto Federal de Educação, Ciência e Tecnologia, Rio de Janeiro, RJ, Brazil
  5. 5Instituto Nacional de Câncer, Divisão de Farmacologia, Rio de Janeiro, Brazil
  6. 6Genetics and Population Health Division, QIMR, BNE, Brisbane, Queensland, Australia
  7. 7Department of Human Genetics, Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, the Netherlands
  8. 8Service de Génétique, Institut Curie, Hôpital René Huguenin, Paris, France
  9. 9Institut Curie, Université Pierre et Marie Curie, Paris, France
  10. 10Fundación Pública Galega de Medicina Xenómica, Santiago, Spain
  11. 11Department of Biochemistry, University of Alberta, Alberta, Canada
  12. 12Instituto di Fisiologia Clinica, Consiglio Nazionale delle Ricerche, Pisa, Italy
  13. 13University of Southampton, Southampton, UK
  14. 14Department of Clinical Genetics, Maastricht University Medical Centre, Maastricht, the Netherlands
  15. 15Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands
  16. 16CIBERER, Madrid, Spain
  17. 17Department of Population Sciences, Beckman Research Institute of the City of Hope, Duarte, California, USA
  18. 18University of Miami Medical School, Miami, Florida, USA
  19. 19Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno, Czech Republic
  20. 20Salisbury District Hospital, Salisbury, Wiltshire, UK
  21. 21International Agency for Research on Cancer, Lyon, France
  22. 22Department of Laboratory Medicine and Pathology, and Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA
  23. 23Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah, USA
  24. 24Genome Technology Branch, National Human Genome Research Institute, Bethesda, Maryland, USA
  25. 25Center for Cancer Research, National Cancer Institute, Frederick, Maryland, USA
  1. Correspondence to Dr Alvaro N Monteiro, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA; alvaro.monteiro{at}


Background Inactivating germline mutations in the tumour suppressor gene BRCA1 are associated with a significantly increased risk of developing breast and ovarian cancer. A large number (>1500) of unique BRCA1 variants have been identified in the population and can be classified as pathogenic, non-pathogenic or as variants of unknown significance (VUS). Many VUS are rare missense variants leading to single amino acid changes. Their impact on protein function cannot be directly inferred from sequence information, precluding assessment of their pathogenicity. Thus, functional assays are critical to assess the impact of these VUS on protein activity. BRCA1 is a multifunctional protein and different assays have been used to assess the impact of variants on different biochemical activities and biological processes.

Methods and results To facilitate VUS analysis, we have developed a visualisation resource that compiles and displays functional data on all documented BRCA1 missense variants. BRCA1 Circos is a web-based visualisation tool based on the freely available Circos software package. The BRCA1 Circos web tool ( aggregates data from all published BRCA1 missense variants for functional studies, harmonises their results and presents various functionalities to search and interpret individual-level functional information for each BRCA1 missense variant.

Conclusions This research visualisation tool will serve as a quick one-stop publically available reference for all the BRCA1 missense variants that have been functionally assessed. It will facilitate meta-analysis of functional data and improve assessment of pathogenicity of VUS.

  • Cancer: breast
  • Clinical genetics
  • Molecular genetics
  • BRCA1

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