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International Journal of Breast Cancer
Volume 2016, Article ID 2469523, 10 pages
Review Article

Beyond DNA: An Integrated and Functional Approach for Classifying Germline Variants in Breast Cancer Genes

Ambry Genetics Corp., 15 Argonaut, Aliso Viejo, CA 92656, USA

Received 4 June 2016; Revised 4 September 2016; Accepted 19 September 2016

Academic Editor: Zsuzsanna Kahán

Copyright © 2016 T. Pesaran et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Genetic testing for hereditary breast cancer is an integral part of individualized care in the new era of precision medicine. The accuracy of an assay is reliant on not only the technology and bioinformatics analysis utilized but also the experience and infrastructure required to correctly classify genetic variants as disease-causing. Interpreting the clinical significance of germline variants identified by hereditary cancer testing is complex and has a significant impact on the management of patients who are at increased cancer risk. In this review we give an overview of our clinical laboratory’s integrated approach to variant assessment. We discuss some of the nuances that should be considered in the assessment of genomic variants. In addition, we highlight lines of evidence such as functional assays and structural analysis that can be useful in the assessment of rare and complex variants.