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.