Journal article

Contribution of mRNA Splicing to Mismatch Repair Gene Sequence Variant Interpretation.

Bryony A Thompson, Rhiannon Walters, Michael T Parsons, Troy Dumenil, Mark Drost, Yvonne Tiersma, Noralane M Lindor, Sean V Tavtigian, Niels de Wind, Amanda B Spurdle, undefined InSiGHT Variant Interpretation Committee

Frontiers in Genetics | Published : 2020


Functional assays that assess mRNA splicing can be used in interpretation of the clinical significance of sequence variants, including the Lynch syndrome-associated mismatch repair (MMR) genes. The purpose of this study was to investigate the contribution of splicing assay data to the classification of MMR gene sequence variants. We assayed mRNA splicing for 24 sequence variants in MLH1, MSH2, and MSH6, including 12 missense variants that were also assessed using a cell-free in vitro MMR activity (CIMRA) assay. Multifactorial likelihood analysis was conducted for each variant, combining CIMRA outputs and clinical data where available. We collated these results with existing public data to pr..

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University of Melbourne Researchers