INVUSE: Investigating Variants of Uncertain Significance for Use in clinical practice

Hein te Riele1, Niels de Wind2, Rolf Sijmons3, on behalf of the INVUSE consortium

1Division of Tumor Biology and Immunology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. Phone +31-20-5122084; Email

2Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

3Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands


To implement functional assays in clinical practice, we created a nationwide consortium of health care professionals and researchers responsible for and interested in the care of patients and families with Lynch syndrome. The consortium, termed INVUSE: investigating variants of uncertain significance for use in clinical practice”, comprises preclinical researchers, clinical geneticists, clinical laboratory geneticists, pathologists and gastroenterologists from the eight Dutch academic medical centers and the Netherlands Cancer Institute, and is financially supported by the Dutch Cancer Society.


Two independent and complementary functional tests, CIMRA and ODMS will be transferred to clinical genetics laboratories where they will be performed as a diagnostic test that is part of a clinical diagnosis and treatment trajectory. Participating institutes can request functional testing by depositing VUS on a protected website. The test results and all clinical information available will then be posted on the website and be used for classification of VUS according to the InSiGHT classification scheme during regular plenary consortium meetings. In addition, an estimation will be made on the severity of the mutation, which may have consequences for the instalment of proper surveillance programs for mutation carriers.