Journal article

Assessment of the InSiGHT Interpretation Criteria for the Clinical Classification of 24 MLH1 and MSH2 Gene Variants

Rossella Tricarico, Mariann Kasela, Cristina Mareni, Bryony A Thompson, Aurelie Drouet, Lucia Staderini, Greta Gorelli, Francesca Crucianelli, Valentina Ingrosso, Jukka Kantelinen, Laura Papi, Maria De Angioletti, Margherita Berardi, Pascaline Gaildrat, Omar Soukarieh, Daniela Turchetti, Alexandra Martins, Amanda B Spurdle, Minna Nystrom, Maurizio Genuardi

Human Mutation | WILEY | Published : 2017


Pathogenicity assessment of DNA variants in disease genes to explain their clinical consequences is an integral component of diagnostic molecular testing. The International Society for Gastrointestinal Hereditary Tumors (InSiGHT) has developed specific criteria for the interpretation of mismatch repair (MMR) gene variants. Here, we performed a systematic investigation of 24 MLH1 and MSH2 variants. The assessments were done by analyzing population frequency, segregation, tumor molecular characteristics, RNA effects, protein expression levels, and in vitro MMR activity. Classifications were confirmed for 15 variants and changed for three, and for the first time determined for six novel variant..

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University of Melbourne Researchers


Awarded by NHMRC Early Career Fellowship

Awarded by NHMRC

Awarded by NIH

Awarded by European Research Council

Funding Acknowledgements

Contract grant sponsors: Istituto Toscano Tumori (ITT); NHMRC Early Career Fellowship (ID1091211); NHMRC Senior Research Fellowship (ID1061779); NIH (grant ID NIH R01CA164944); European Research Council (2008-AdG-232635); French Institut National du Cancer/Direction Generale de l'Offre de Soins (INCa/DGOS); Fondation ARC pour la Recherche sur le Cancer; French Ministry of Education