PT - JOURNAL ARTICLE AU - Ankita Jhuraney AU - Aneliya Velkova AU - Randall C Johnson AU - Bailey Kessing AU - Renato S Carvalho AU - Phillip Whiley AU - Amanda B Spurdle AU - Maaike P G Vreeswijk AU - Sandrine M Caputo AU - Gael A Millot AU - Ana Vega AU - Nicolas Coquelle AU - Alvaro Galli AU - Diana Eccles AU - Marinus J Blok AU - Tuya Pal AU - Rob B van der Luijt AU - Marta Santamariña Pena AU - Susan L Neuhausen AU - Talia Donenberg AU - Eva Machackova AU - Simon Thomas AU - Maxime Vallée AU - Fergus J Couch AU - Sean V Tavtigian AU - J N Mark Glover AU - Marcelo A Carvalho AU - Lawrence C Brody AU - Shyam K Sharan AU - Alvaro N Monteiro AU - on behalf of the ENIGMA (Evidence-based Network for the Interpretation of Germline Mutant Alleles) Consortium TI - BRCA1 Circos: a visualisation resource for functional analysis of missense variants AID - 10.1136/jmedgenet-2014-102766 DP - 2015 Apr 01 TA - Journal of Medical Genetics PG - 224--230 VI - 52 IP - 4 4099 - http://jmg.bmj.com/content/52/4/224.short 4100 - http://jmg.bmj.com/content/52/4/224.full SO - J Med Genet2015 Apr 01; 52 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.