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 Jhuraney, Ankita A1 Velkova, Aneliya A1 Johnson, Randall C A1 Kessing, Bailey A1 Carvalho, Renato S A1 Whiley, Phillip A1 Spurdle, Amanda B A1 Vreeswijk, Maaike P G A1 Caputo, Sandrine M A1 Millot, Gael A A1 Vega, Ana A1 Coquelle, Nicolas A1 Galli, Alvaro A1 Eccles, Diana A1 Blok, Marinus J A1 Pal, Tuya A1 van der Luijt, Rob B A1 Santamariña Pena, Marta A1 Neuhausen, Susan L A1 Donenberg, Talia A1 Machackova, Eva A1 Thomas, Simon A1 Vallée, Maxime A1 Couch, Fergus J A1 Tavtigian, Sean V A1 Glover, J N Mark A1 Carvalho, Marcelo A A1 Brody, Lawrence C A1 Sharan, Shyam K A1 Monteiro, Alvaro N 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.