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Leiden open variation database of the MUTYH gene

Identifieur interne : 001340 ( Istex/Curation ); précédent : 001339; suivant : 001341

Leiden open variation database of the MUTYH gene

Auteurs : Astrid A. Out [Pays-Bas] ; Carli M. J. Tops [Pays-Bas] ; Maartje Nielsen [Pays-Bas] ; Marjan M. Weiss [Pays-Bas] ; Ivonne J. H. M. Van Minderhout [Pays-Bas] ; Ivo F. A. C. Fokkema [Pays-Bas] ; Marie-Pierre Buisine [France] ; Kathleen Claes [Belgique] ; Chrystelle Colas [France] ; Riccardo Fodde [Pays-Bas] ; Florentia Fostira [Grèce] ; Patrick F. Franken [Pays-Bas] ; Mette Gaustadnes [Danemark] ; Karl Heinimann [Suisse] ; Shirley V. Hodgson [Royaume-Uni] ; Frans B. L. Hogervorst [Pays-Bas] ; Elke Holinski-Feder [Allemagne] ; Kristina Lagerstedt-Robinson [Suède] ; Sylviane Olschwang [France] ; Van Den Ouweland Ans M. W. [Pays-Bas] ; Egbert J. W. Redeker [Pays-Bas] ; Rodney J. Scott [Australie] ; Bruno Vankeirsbilck [Belgique] ; Rikke Veggerby Gr Nlund [Danemark] ; Juul T. Wijnen [Pays-Bas] ; Friedrik P. Wikman [Danemark] ; Stefan Aretz [Allemagne] ; Julian R. Sampson [Royaume-Uni] ; Peter Devilee [Pays-Bas] ; Johan T. Den Dunnen [Pays-Bas] ; Frederik J. Hes [Pays-Bas]

Source :

RBID : ISTEX:67661BEDECD2819B51432F0F9E9B0C811AE72E3B

Descripteurs français

English descriptors

Abstract

The MUTYH gene encodes a DNA glycosylase involved in base excision repair (BER). Biallelic pathogenic MUTYH variants have been associated with colorectal polyposis and cancer. The pathogenicity of a few variants is beyond doubt, including c.536A>G/p.Tyr179Cys and c.1187G>A/p.Gly396Asp (previously c.494A>G/p.Tyr165Cys and c.1145G>A/p.Gly382Asp). However, for a substantial fraction of the detected variants, the clinical significance remains uncertain, compromising molecular diagnostics and thereby genetic counseling. We have established an interactive MUTYH gene sequence variant database (www.lovd.nl/MUTYH) with the aim of collecting and sharing MUTYH genotype and phenotype data worldwide. To support standard variant description, we chose NM_001128425.1 as the reference sequence. The database includes records with variants per individual, linked to available phenotype and geographic origin data as well as records with in vitro functional and in silico test data. As of April 2010, the database contains 1968 published and 423 unpublished submitted entries, and 230 and 61 unique variants, respectively. This open‐access repository allows all involved to quickly share all variants encountered and communicate potential consequences, which will be especially useful to classify variants of uncertain significance. Hum Mutat 31:1–11, 2010. © 2010 Wiley‐Liss, Inc.

Url:
DOI: 10.1002/humu.21343

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ISTEX:67661BEDECD2819B51432F0F9E9B0C811AE72E3B

Le document en format XML

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<mods:affiliation>Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands</mods:affiliation>
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<name sortKey="Fokkema, Ivo F A C" sort="Fokkema, Ivo F A C" uniqKey="Fokkema I" first="Ivo F. A. C." last="Fokkema">Ivo F. A. C. Fokkema</name>
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<mods:affiliation>Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands</mods:affiliation>
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<name sortKey="Buisine, Marie Ierre" sort="Buisine, Marie Ierre" uniqKey="Buisine M" first="Marie-Pierre" last="Buisine">Marie-Pierre Buisine</name>
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<name sortKey="Claes, Kathleen" sort="Claes, Kathleen" uniqKey="Claes K" first="Kathleen" last="Claes">Kathleen Claes</name>
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<name sortKey="Fodde, Riccardo" sort="Fodde, Riccardo" uniqKey="Fodde R" first="Riccardo" last="Fodde">Riccardo Fodde</name>
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<mods:affiliation>Department of Pathology, Josephine Nefkens Institute, Erasmus University Medical Center, Rotterdam, The Netherlands</mods:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pathology, Josephine Nefkens Institute, Erasmus University Medical Center, Rotterdam</wicri:regionArea>
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<name sortKey="Fostira, Florentia" sort="Fostira, Florentia" uniqKey="Fostira F" first="Florentia" last="Fostira">Florentia Fostira</name>
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<name sortKey="Franken, Patrick F" sort="Franken, Patrick F" uniqKey="Franken P" first="Patrick F." last="Franken">Patrick F. Franken</name>
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<wicri:regionArea>Department of Pathology, Josephine Nefkens Institute, Erasmus University Medical Center, Rotterdam</wicri:regionArea>
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<name sortKey="Gaustadnes, Mette" sort="Gaustadnes, Mette" uniqKey="Gaustadnes M" first="Mette" last="Gaustadnes">Mette Gaustadnes</name>
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<country xml:lang="fr">Suisse</country>
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<name sortKey="Hodgson, Shirley V" sort="Hodgson, Shirley V" uniqKey="Hodgson S" first="Shirley V." last="Hodgson">Shirley V. Hodgson</name>
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<name sortKey="Hogervorst, Frans B L" sort="Hogervorst, Frans B L" uniqKey="Hogervorst F" first="Frans B. L." last="Hogervorst">Frans B. L. Hogervorst</name>
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<name sortKey="Holinski Eder, Elke" sort="Holinski Eder, Elke" uniqKey="Holinski Eder E" first="Elke" last="Holinski-Feder">Elke Holinski-Feder</name>
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<mods:affiliation>University Hospital of the Ludwig‐Maximilians‐University, Campus Innenstadt, Munich, Germany</mods:affiliation>
<country xml:lang="fr">Allemagne</country>
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<name sortKey="Lagerstedt Obinson, Kristina" sort="Lagerstedt Obinson, Kristina" uniqKey="Lagerstedt Obinson K" first="Kristina" last="Lagerstedt-Robinson">Kristina Lagerstedt-Robinson</name>
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<mods:affiliation>Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden</mods:affiliation>
<country xml:lang="fr">Suède</country>
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<name sortKey="Olschwang, Sylviane" sort="Olschwang, Sylviane" uniqKey="Olschwang S" first="Sylviane" last="Olschwang">Sylviane Olschwang</name>
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<mods:affiliation>Inserm, U599, Centre de Recherches en Cancérologie de Marseille, Molecular Oncology, Marseille, France</mods:affiliation>
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<mods:affiliation>Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands</mods:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam</wicri:regionArea>
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<name sortKey="Redeker, Egbert J W" sort="Redeker, Egbert J W" uniqKey="Redeker E" first="Egbert J. W." last="Redeker">Egbert J. W. Redeker</name>
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<mods:affiliation>Department of Clinical Genetics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands</mods:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Clinical Genetics, Academic Medical Centre, University of Amsterdam, Amsterdam</wicri:regionArea>
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<author>
<name sortKey="Scott, Rodney J" sort="Scott, Rodney J" uniqKey="Scott R" first="Rodney J." last="Scott">Rodney J. Scott</name>
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<mods:affiliation>Hunter Medical Research Institute, John Hunter Hospital and Faculty of Medicine and Health Sciences, The University of Newcastle, Newcastle, Australia</mods:affiliation>
<country xml:lang="fr">Australie</country>
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<name sortKey="Vankeirsbilck, Bruno" sort="Vankeirsbilck, Bruno" uniqKey="Vankeirsbilck B" first="Bruno" last="Vankeirsbilck">Bruno Vankeirsbilck</name>
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<mods:affiliation>Center for Human Genetics, University Hospital of Leuven, Belgium</mods:affiliation>
<country xml:lang="fr">Belgique</country>
<wicri:regionArea>Center for Human Genetics, University Hospital of Leuven</wicri:regionArea>
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</author>
<author>
<name sortKey="Gr Nlund, Rikke Veggerby" sort="Gr Nlund, Rikke Veggerby" uniqKey="Gr Nlund R" first="Rikke Veggerby" last="Gr Nlund">Rikke Veggerby Gr Nlund</name>
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<mods:affiliation>Department of Clinical Biochemistry, Hvidovre Hospital, Hvidovre, Denmark</mods:affiliation>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Department of Clinical Biochemistry, Hvidovre Hospital, Hvidovre</wicri:regionArea>
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<name sortKey="Wijnen, Juul T" sort="Wijnen, Juul T" uniqKey="Wijnen J" first="Juul T." last="Wijnen">Juul T. Wijnen</name>
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<mods:affiliation>Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands</mods:affiliation>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Clinical Genetics, Leiden University Medical Center, Leiden</wicri:regionArea>
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<name sortKey="Wikman, Friedrik P" sort="Wikman, Friedrik P" uniqKey="Wikman F" first="Friedrik P." last="Wikman">Friedrik P. Wikman</name>
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<mods:affiliation>Department of Molecular Medicine, Aarhus University Hospital Skejby, Aarhus, Denmark</mods:affiliation>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Department of Molecular Medicine, Aarhus University Hospital Skejby, Aarhus</wicri:regionArea>
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<name sortKey="Aretz, Stefan" sort="Aretz, Stefan" uniqKey="Aretz S" first="Stefan" last="Aretz">Stefan Aretz</name>
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<mods:affiliation>Institute of Human Genetics, University of Bonn, Bonn, Germany</mods:affiliation>
<country xml:lang="fr">Allemagne</country>
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<name sortKey="Sampson, Julian R" sort="Sampson, Julian R" uniqKey="Sampson J" first="Julian R." last="Sampson">Julian R. Sampson</name>
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<mods:affiliation>Institute of Medical Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, United Kingdom</mods:affiliation>
<country xml:lang="fr">Royaume-Uni</country>
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<name sortKey="Devilee, Peter" sort="Devilee, Peter" uniqKey="Devilee P" first="Peter" last="Devilee">Peter Devilee</name>
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<mods:affiliation>Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands</mods:affiliation>
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<name sortKey="Den Dunnen, Johan T" sort="Den Dunnen, Johan T" uniqKey="Den Dunnen J" first="Johan T." last="Den Dunnen">Johan T. Den Dunnen</name>
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<mods:affiliation>Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands</mods:affiliation>
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<title level="j" type="main">Human Mutation</title>
<title level="j" type="alt">HUMAN MUTATION</title>
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<term>Allele frequency</term>
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<term>Alpha5</term>
<term>Amino</term>
<term>Amino acids</term>
<term>Annotation</term>
<term>Assay</term>
<term>Base excision repair</term>
<term>Base excision repair gene</term>
<term>Biallelic</term>
<term>Breast cancer</term>
<term>Carcinoma</term>
<term>Cleary</term>
<term>Clin oncol</term>
<term>Clinical genetics</term>
<term>Coding exons</term>
<term>Coding reference sequence</term>
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<term>Coli</term>
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<term>Colorectal cancer</term>
<term>Colorectal cancer risk</term>
<term>Colorectal carcinomas</term>
<term>Colorectal polyposis</term>
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<term>Database</term>
<term>Database contents</term>
<term>Endometrial cancer</term>
<term>Erasmus university</term>
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<term>Familial adenomatous polyposis</term>
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<term>Functional domains</term>
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<term>Gastric cancer</term>
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<term>Gene databases</term>
<term>Genet</term>
<term>Genetic counseling</term>
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<term>Genetics</term>
<term>Germline</term>
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<term>Germline variants</term>
<term>Glycosylase</term>
<term>Hepatocellular carcinoma</term>
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<term>Human muty</term>
<term>Human muty homolog</term>
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<term>Isoforms</term>
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<term>Leiden university</term>
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<term>Phenotype data</term>
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<term>Reference sequence</term>
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<term>Silico analyses</term>
<term>Silico test data</term>
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<term>Splice</term>
<term>Splice variant</term>
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<term>Supp</term>
<term>Test results</term>
<term>Transcript</term>
<term>Transcript alpha5</term>
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<term>Alpha5</term>
<term>Amino</term>
<term>Amino acids</term>
<term>Annotation</term>
<term>Assay</term>
<term>Base excision repair</term>
<term>Base excision repair gene</term>
<term>Biallelic</term>
<term>Breast cancer</term>
<term>Carcinoma</term>
<term>Cleary</term>
<term>Clin oncol</term>
<term>Clinical genetics</term>
<term>Coding exons</term>
<term>Coding reference sequence</term>
<term>Codon</term>
<term>Coli</term>
<term>Colorectal</term>
<term>Colorectal cancer</term>
<term>Colorectal cancer risk</term>
<term>Colorectal carcinomas</term>
<term>Colorectal polyposis</term>
<term>Colorectal tumors</term>
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<term>Database contents</term>
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<term>Functional characterization</term>
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<term>Gamma transcripts</term>
<term>Gastric cancer</term>
<term>Gene</term>
<term>Gene databases</term>
<term>Genet</term>
<term>Genetic counseling</term>
<term>Genetic variation</term>
<term>Genetics</term>
<term>Germline</term>
<term>Germline mutations</term>
<term>Germline variants</term>
<term>Glycosylase</term>
<term>Hepatocellular carcinoma</term>
<term>Hmyh</term>
<term>Homolog</term>
<term>Human genetics</term>
<term>Human mutation</term>
<term>Human muty</term>
<term>Human muty homolog</term>
<term>Human mutyh gene</term>
<term>Isoform</term>
<term>Isoforms</term>
<term>Largest isoform</term>
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<term>Leiden university</term>
<term>Lovd</term>
<term>Lovd database</term>
<term>Lovd format</term>
<term>Lovd software</term>
<term>Mature mrnas</term>
<term>Medical genetics</term>
<term>Missense</term>
<term>Missense variants</term>
<term>Multiple genes</term>
<term>Mutat</term>
<term>Mutation</term>
<term>Muty</term>
<term>Muty homolog</term>
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<term>Mutyh lovd</term>
<term>Mutyh protein</term>
<term>Mutyh variants</term>
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<term>Nucleic acids</term>
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<term>Pathogenic variants</term>
<term>Pathogenicity</term>
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<term>Reference sequence</term>
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<term>Silico analyses</term>
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<term>Splice</term>
<term>Splice variant</term>
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<term>Supp</term>
<term>Test results</term>
<term>Transcript</term>
<term>Transcript alpha5</term>
<term>Uncertain significance</term>
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<term>Unpublished data</term>
<term>Variant</term>
<term>Variant pathogenicity</term>
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<div type="abstract" xml:lang="en">The MUTYH gene encodes a DNA glycosylase involved in base excision repair (BER). Biallelic pathogenic MUTYH variants have been associated with colorectal polyposis and cancer. The pathogenicity of a few variants is beyond doubt, including c.536A>G/p.Tyr179Cys and c.1187G>A/p.Gly396Asp (previously c.494A>G/p.Tyr165Cys and c.1145G>A/p.Gly382Asp). However, for a substantial fraction of the detected variants, the clinical significance remains uncertain, compromising molecular diagnostics and thereby genetic counseling. We have established an interactive MUTYH gene sequence variant database (www.lovd.nl/MUTYH) with the aim of collecting and sharing MUTYH genotype and phenotype data worldwide. To support standard variant description, we chose NM_001128425.1 as the reference sequence. The database includes records with variants per individual, linked to available phenotype and geographic origin data as well as records with in vitro functional and in silico test data. As of April 2010, the database contains 1968 published and 423 unpublished submitted entries, and 230 and 61 unique variants, respectively. This open‐access repository allows all involved to quickly share all variants encountered and communicate potential consequences, which will be especially useful to classify variants of uncertain significance. Hum Mutat 31:1–11, 2010. © 2010 Wiley‐Liss, Inc.</div>
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