RT Journal Article SR Electronic T1 BRCA1 Circos: a visualisation resource for functional analysis of missense variants JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 224 OP 230 DO 10.1136/jmedgenet-2014-102766 VO 52 IS 4 A1 Ankita Jhuraney A1 Aneliya Velkova A1 Randall C Johnson A1 Bailey Kessing A1 Renato S Carvalho A1 Phillip Whiley A1 Amanda B Spurdle A1 Maaike P G Vreeswijk A1 Sandrine M Caputo A1 Gael A Millot A1 Ana Vega A1 Nicolas Coquelle A1 Alvaro Galli A1 Diana Eccles A1 Marinus J Blok A1 Tuya Pal A1 Rob B van der Luijt A1 Marta Santamariña Pena A1 Susan L Neuhausen A1 Talia Donenberg A1 Eva Machackova A1 Simon Thomas A1 Maxime Vallée A1 Fergus J Couch A1 Sean V Tavtigian A1 J N Mark Glover A1 Marcelo A Carvalho A1 Lawrence C Brody A1 Shyam K Sharan A1 Alvaro N Monteiro A1 on behalf of the ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) Consortium YR 2015 UL http://jmg.bmj.com/content/52/4/224.abstract AB 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 (http://research.nhgri.nih.gov/bic/circos/) 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.