Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database

Nature Genetics
Bryony A ThompsonMaurizio Genuardi

Abstract

The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and apply a standardized classification scheme to constitutional variants in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2. Unpublished data submission was encouraged to assist in variant classification and was recognized through microattribution. The scheme was refined by multidisciplinary expert committee review of the clinical and functional data available for variants, applied to 2,360 sequence alterations, and disseminated online. Assessment using validated criteria altered classifications for 66% of 12,006 database entries. Clinical recommendations based on transparent evaluation are now possible for 1,370 variants that were not obviously protein truncating from nomenclature. This large-scale endeavor will facilitate the consistent management of families suspected to have Lynch syndrome and demonstrates the value of multidisciplinary collaboration in the curation and classification of variants in public locus-specific d...Continue Reading

References

Aug 6, 2003·American Journal of Human Genetics·Deborah ThompsonDavid E Goldgar
Feb 19, 2004·Journal of the National Cancer Institute·Asad UmarSudhir Srivastava
Apr 26, 2005·International Journal of Cancer. Journal International Du Cancer·Elisabeth MangoldPeter Propping
Jun 30, 2006·The New England Journal of Medicine·Rebecca A BarnetsonMalcolm G Dunlop
Mar 10, 2007·Human Mutation·Michael O WoodsH Banfield Younghusband
May 17, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Leeanne J MeadMelissa C Southey
May 19, 2007·Cancer Research·Masanobu TakahashiChikashi Ishioka
Apr 17, 2008·Genetics in Medicine : Official Journal of the American College of Medical Genetics·C Sue RichardsUNKNOWN Molecular Subcommittee of the ACMG Laboratory Quality Assurance Committee
Jul 8, 2008·Gastroenterology·Leigha SenterAlbert de la Chapelle
Oct 28, 2008·Human Mutation·Sean V TavtigianUNKNOWN IARC Unclassified Genetic Variants Working Group
Oct 28, 2008·Human Mutation·David E GoldgarUNKNOWN IARC Unclassified Genetic Variants Working Group
Oct 28, 2008·Human Mutation·Marc S GreenblattUNKNOWN IARC Unclassified Genetic Variants Working Group
Oct 28, 2008·Human Mutation·Sharon E PlonUNKNOWN IARC Unclassified Genetic Variants Working Group
Oct 28, 2008·Human Mutation·Amanda B SpurdleUNKNOWN IARC Unclassified Genetic Variants Working Group
Oct 28, 2008·Human Mutation·Fergus J CouchUNKNOWN IARC Unclassified Genetic Variants Working Group
Sep 2, 2009·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Heikki J JärvinenJukka-Pekka Mecklin
Sep 3, 2009·Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology·Eli Marie GrindedalLovise Maehle
Dec 24, 2009·Journal of the National Cancer Institute·Laura BagliettoMark A Jenkins
Jul 14, 2010·Proceedings of the National Academy of Sciences of the United States of America·Johanna M M van OersWinfried Edelmann
Oct 28, 2010·Cancer Prevention Research·Jenny XieSharon B Cantor
Oct 29, 2010·Nature·Gonçalo R AbecasisGil A McVean
Mar 10, 2011·Human Mutation·Maija R J Kohonen-CorishUNKNOWN Contributors to the InSiGHT-HVP Workshop
Jun 7, 2011·JAMA : the Journal of the American Medical Association·Valérie BonadonaUNKNOWN French Cancer Genetics Network
Oct 13, 2011·Human Mutation·Maxime P ValléeSean V Tavtigian
Oct 29, 2011·Genes, Chromosomes & Cancer·Nicole BuerkiKarl Heinimann
Feb 15, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Aung Ko WinMark A Jenkins
Jul 25, 2012·Hereditary Cancer in Clinical Practice·Christopher D Heinen, Lene Juel Rasmussen
Aug 15, 2012·Journal of Medical Genetics·Amanda B SpurdleUNKNOWN ENIGMA Consortium
Aug 31, 2012·Journal of the National Cancer Institute·Aung Ko WinMark A Jenkins

❮ Previous
Next ❯

Citations

Jun 24, 2014·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Adela CastillejoJosé Luis Soto
Sep 23, 2014·Health Technology Assessment : HTA·Tristan SnowsillChris Hyde
Jan 19, 2016·Frontiers in Microbiology·Abdullah F SaeedShihua Wang
Dec 19, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Lisa R SussweinWendy K Chung
Dec 19, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Wei SongNarasimhan Nagan
Dec 2, 2014·Epigenetics : Official Journal of the DNA Methylation Society·Francesca CrucianelliMaurizio Genuardi
Feb 20, 2016·Expert Review of Molecular Diagnostics·Natalia BuzaPei Hui
Feb 28, 2015·Genome Medicine·Ingrid SladeUNKNOWN MCG programme
May 28, 2015·The New England Journal of Medicine·Heidi L RehmUNKNOWN ClinGen
Jun 4, 2015·European Journal of Human Genetics : EJHG·Jayne Y Hehir-KwaPeter N Robinson
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Feb 13, 2015·Nature Reviews. Cancer·Henry T LynchMegan P Hitchins
Sep 6, 2014·Frontiers in Genetics·Sara Thornby BakJavier Pena-Diaz
Aug 8, 2015·PloS One·Jeffery W BacherRichard B Halberg
Nov 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Michael C AdamsJonathan S Berg
Aug 19, 2014·PloS One·Maria A LoizidouKyriacos Kyriacou
Jun 24, 2016·British Journal of Cancer·Synnöve StaffJohanna Mäenpää
Jan 4, 2015·Molecular Genetics and Metabolism·James T BennettSi Houn Hahn
Aug 16, 2016·European Journal of Human Genetics : EJHG·Andrew J Wallace
Nov 11, 2016·Journal of Human Genetics·Maria Teresa RicciLiliana Varesco
Jun 9, 2016·Journal of Gastroenterology and Hepatology·Daniel D BuchananMark A Jenkins
Jul 20, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Nicole de RosaY Nancy You
Dec 24, 2014·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Mark A JenkinsAung Ko Win
Jan 7, 2015·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Daniel ChubbRichard S Houlston
Sep 14, 2016·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Judith BalmañaSusan M Domchek
Feb 23, 2017·Human Mutation·Abhishek Niroula, Mauno Vihinen
May 18, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Carin R EspenschiedHeather Hampel
May 13, 2017·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·Antonios AnagnostopoulosJohn Kirwan
Feb 6, 2017·Current Opinion in Genetics & Development·Derick C HoskinsonHeather Mason-Suares
May 27, 2017·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Shigeki SekineNobuyoshi Hiraoka

❮ Previous
Next ❯

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