Journal article

BRCA1 R1699Q variant displaying ambiguous functional abrogation confers intermediate breast and ovarian cancer risk

Amanda B Spurdle, Phillip J Whiley, Bryony Thompson, Bingjian Feng, Sue Healey, Melissa A Brown, Christopher Pettigrew, Christi J Van Asperen, Margreet GEM Ausems, Anna A Kattentidt-Mouravieva, Ans MW van den Ouweland, Annika Lindblom, Maritta H Pigg, Rita K Schmutzler, Christoph Engel, Alfons Meindl, Sandrine Caputo, Olga M Sinilnikova, Rosette Lidereau, Fergus J Couch Show all



BACKGROUND: Clinical classification of rare sequence changes identified in the breast cancer susceptibility genes BRCA1 and BRCA2 is essential for appropriate genetic counselling of individuals carrying these variants. We previously showed that variant BRCA1 c.5096G>A p.Arg1699Gln in the BRCA1 transcriptional transactivation domain demonstrated equivocal results from a series of functional assays, and proposed that this variant may confer low to moderate risk of cancer. METHODS: Measures of genetic risk (report of family history, segregation) were assessed for 68 BRCA1 c.5096G>A p.Arg1699Gln (R1699Q) families recruited through family cancer clinics, comparing results with 34 families carryin..

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University of Melbourne Researchers


Awarded by NHMRC

Awarded by Canadian Institutes of Health Research Team Grant in Familial Risks of Breast Cancer

Awarded by German Cancer Aid

Awarded by NIH

Awarded by Dutch Cancer Society

Awarded by National Institutes of Health Recovery Act supplement award


Funding Acknowledgements

This work was supported in part by project grants from The National Health and Medical Research Council (NHMRC) to ABS. ABS is supported by an NHMRC Senior Research Fellowship. kConFab is supported by grants from the National Breast Cancer Foundation, the NHMRC and by the Queensland Cancer Fund, the Cancer Councils of New South Wales, Victoria, Tasmania and South Australia, and the Cancer Foundation of Western Australia. The kConFab Clinical Follow Up Study was funded by NHMRC grants (145684 and 288704). BJF is supported by the Canadian Institutes of Health Research Team Grant in Familial Risks of Breast Cancer CRN-87521. AL thanks the Swedish Cancer Society for support. The work of the German Consortium GC-HBOC is supported by a grant of the German Cancer Aid (grant 107364, RKS) and by the Centre for Molecular Medicine Cologne, Cologne, Germany (RKS, BW). The French Consortium thanks the Association d'Aide a la Recherche Cancerologique de Saint Cloud (ARCs) and the Ligue 92 contre le Cancer for their financial support. FJC and DEG are supported by NIH grant CA116167, an NIH Recovery Act supplement (CA116167Z), and an NIH Specialised Programme of Research Excellence (SPORE) in Breast Cancer (CA116201). LG is supported by a Komen Race for the Cure Fellowship. Research by TvOH was supported by the NEYE Foundation. SMD is supported by funding from the Komen Foundation for the Cure. Ohio State University CCG is supported by the OSU Comprehensive Cancer Center (AET). EJVR is funded by grants from the Cancer Association of South Africa. The research coordinated by MPGV was supported by Dutch Cancer Society grants 2001-2471 and 2006-3677. DEG is supported by NIH grant CA116167. Coordination of ENIGMA is funded by The National Institutes of Health Recovery Act supplement award (CA116167Z).