Athena Insight: Building a Better Understanding of Variants of Unknown Significance

Dr. Izabela Karbassi Collaborates with Dr. Mark Nellist to Better Understand the Effect of Variants of Unknown Significance on Protein Structures

As genetic testing and its significance play a more significant role in patient diagnosis and management, the Athena Insight program yields powerful tools to help better understand the importance of variants of unknown significance.

Athena Diagnostics leads the field in interpreting genetic test results, and the investigation staff has helped providers andpatients alike glean more information than ever before.

The Athena Insight team maintains its leadership position by proactively seeking the world’s experts in genetics and working side-by-side to better interpret results.

Recently, Dr. Izabela Karbassi, Scientist for Athena Diagnostics’ Insight Variant Investigative Team (VIT), studied genes and the resulting protein structures to develop a list of suspect variants that would more than likely be damaging to the protein function. She shared the list with, Dr. Petrou, a collaborator in Australia, who is currently working on evaluating these variants through both mathematical predictive algorithms as well as wet bench functional assays.

In addition, Dr. Karbassi presented her findings on SCN1B sequence variants at the November 2010 American Society of Human Genetics Conference. Dr. Karbassi’s paper is but one of many that the Athena VIT presented, showcasing their understanding of the significance of test data. Working with researchers and key thought leaders from around the world is imperative especially when investigating variants that are rare or unique.

During her analysis, Dr. Karbassi evaluated a variant that she believed could be deleterious to function based on its location in the TSC2 protein. Unable to classify the unknown variant with her existing data, she initiated a consultation with genetic expert, Dr. Mark D. Nellist from the Department of Clinical Genetics at Erasmus Medical Centre in Rotterdam, The Netherlands. She sought out Dr. Nellist based on his success in developing a rapidly reproducible assay to characterize variants. Dr. Karbassi and Dr. Nellist discussed his functional assay in light of the uniqueness of her observations. By taking the initiative upon herself to exchange ideas with Dr. Nellist, Dr. Karbassi hoped to move one step closer to identifying a piece of the puzzle, categorizing the unique variant.

While the collaboration has been successful, some VUS will remain unclassified due to limitations of available information. The goal of the VIT is to research each VUS according to a validated investigation and reporting process. Making use of worldwide data to seek out useful results substantiates the perseverance and resolve of the Athena Variant Investigative Team to discern the unknown and isolate relevant clinical data to classify variants as benign or pathogenic. Ultimately, physicians can share a more comprehensive clinical picture with their patients, adjust treatment, and further understand patient and family genetics.

Working with industry leaders and cutting edge diagnosticians, Athena Diagnostics’ Insight Team Leaders like Dr. Karbassi will continue to have a major impact upon the lives of physicians, patients and their families.

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