<?xml version="1.0" encoding="UTF-8"?><xml><records><record><source-app name="Biblio" version="7.x">Drupal-Biblio</source-app><ref-type>17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Delimitsou,A.</style></author><author><style face="normal" font="default" size="100%">Fostira, F.</style></author><author><style face="normal" font="default" size="100%">Kalfakakou,D.</style></author><author><style face="normal" font="default" size="100%">Apostolou, P.</style></author><author><style face="normal" font="default" size="100%">Konstantopoulou, I.</style></author><author><style face="normal" font="default" size="100%">Kroupis, C.</style></author><author><style face="normal" font="default" size="100%">Papavassiliou, A.G.</style></author><author><style face="normal" font="default" size="100%">Kleibl,Z.</style></author><author><style face="normal" font="default" size="100%">Stratikos,E.</style></author><author><style face="normal" font="default" size="100%">Voutsinas, G.E.</style></author><author><style face="normal" font="default" size="100%">Yannoukakos, D.</style></author></authors></contributors><titles><title><style face="normal" font="default" size="100%">Functional characterization of CHEK2 variants in a Saccharomyces cerevisiae system</style></title><secondary-title><style face="normal" font="default" size="100%">Hum.Mutat.</style></secondary-title></titles><keywords><keyword><style  face="normal" font="default" size="100%">Alleles</style></keyword><keyword><style  face="normal" font="default" size="100%">Amino Acid Substitution</style></keyword><keyword><style  face="normal" font="default" size="100%">Checkpoint Kinase 2</style></keyword><keyword><style  face="normal" font="default" size="100%">Computational Biology</style></keyword><keyword><style  face="normal" font="default" size="100%">Gene Frequency</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Association Studies</style></keyword><keyword><style  face="normal" font="default" size="100%">Genetic Predisposition to Disease</style></keyword><keyword><style  face="normal" font="default" size="100%">genetics</style></keyword><keyword><style  face="normal" font="default" size="100%">Greece</style></keyword><keyword><style  face="normal" font="default" size="100%">Humans</style></keyword><keyword><style  face="normal" font="default" size="100%">metabolism</style></keyword><keyword><style  face="normal" font="default" size="100%">methods</style></keyword><keyword><style  face="normal" font="default" size="100%">Models,Molecular</style></keyword><keyword><style  face="normal" font="default" size="100%">Mutation</style></keyword><keyword><style  face="normal" font="default" size="100%">Pedigree</style></keyword><keyword><style  face="normal" font="default" size="100%">Protein Conformation</style></keyword><keyword><style  face="normal" font="default" size="100%">Saccharomyces cerevisiae</style></keyword></keywords><dates><year><style  face="normal" font="default" size="100%">2019</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2019/05//</style></date></pub-dates></dates><urls><web-urls><url><style face="normal" font="default" size="100%">PM:30851065</style></url></web-urls></urls><volume><style face="normal" font="default" size="100%">40</style></volume><pages><style face="normal" font="default" size="100%">631 - 648</style></pages><language><style face="normal" font="default" size="100%">eng</style></language><abstract><style face="normal" font="default" size="100%">Genetic testing for cancer predisposition leads to the identification of a number of variants with uncertain significance. To some extent, variants of BRCA1/2 have been classified, in contrast to variants of other genes. CHEK2 is a typical example, in which a large number of variants of unknown clinical significance were identified and still remained unclassified. Herein, the CHEK2 variant assessment was performed through an in vivo, yeast-based, functional assay. In total, 120 germline CHEK2 missense variants, distributed along the protein sequence, and two large in-frame deletions were tested, originating from genetic test results in breast cancer families, or selected from the ClinVar database. Of these, 32 missense and two in-frame deletions behaved as non-functional, 73 as functional, and 15 as semi-functional, after comparing growth rates of each strain with positive and negative controls. The majority of non-functional variants were localized in the CHK2 kinase and forkhead-associated domains. In vivo results from the non-functional variants were in agreement with in silico predictions, and, where available, with strong breast cancer family history, to a great extent. The results of the largest, to date, yeast-based assay, evaluating CHEK2 variants, can complement and assist in the classification of rare CHEK2 variants with unclear clinical significance</style></abstract><issue><style face="normal" font="default" size="100%">5</style></issue><notes><style face="normal" font="default" size="100%">IS - 1098-1004 (Electronic)IS - 1059-7794 (Linking)LA - engPT - Journal ArticlePT - Research Support, Non-U.S. Gov'tRN - EC 2.7.1.11 (Checkpoint Kinase 2)RN - EC 2.7.11.1 (CHEK2 protein, human)SB - IM</style></notes></record></records></xml>