N66: The ICCon Australian Database Of Mismatch Repair Variants

F. Macrae1, J. P. Plazzer1, B. Thompson2, A. B. Spurdle3, G. Mitchell4, P. James5

1 – Dept of Colorectal Medicine and Genetics, The Royal Melbourne Hospital. 2 – School of Population Health, University of Melbourne, Australia. 3 – QIMR Berghofer Medical Research Institute, Queensland, Australia. 4 – Chair ICCon Investigators. 5 – Head, Parkville precinct Familial Cancer Clinics.

 

Aim: To systematically collect DNA mismatch repair variants identified by clinical testing in Australian families.

Method: Initial attempts through the HVP sourced variants from laboratories by streamlining with Laboratory Information Management Systems. Subsequently, a grant was awarded from the New South Wales Cancer Council to build a database of pathogenic (Class 4 and 5) variants identified in the cancer genes through the familial cancer clinics (FCCs); a collaboration across the clinics (ICCon) was formed to facilitate this.

Results: The ICCon database holds information about MMR gene pathogenic variants in adult carriers as follows: MLH1 124 (90 unique), MSH2 121 (94), MSH6 68 (50), PMS2 36 (25); totalling 349 (259). Ten discordant interpretations between clinics and/or InSiGHT’s classifications were resolved as part of the ICCon process. Importantly, clinical and other data to assist VUSs was accessible from the FCCs.

Conclusion: Sourcing variants via the FCCs has proved feasible.  The ICCon database has contributed to variant  interpretation internationally, including InSiGHT’s Variant Interpretation Committee and, in part, the PLSD. ICCon is working to achieve governance around transforming the variant database to a national registry, to permit changes in counselling, and clinical management, such as when new information emerges through contemporary experience or research.

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