title: Evaluating the quality of Marfan genotype-phenotype correlations in existing FBN1 databases.
abstract: Genetic FBN1 testing is pivotal for confirming the clinical diagnosis of Marfan syndrome. In an effort to evaluate variant causality, FBN1 databases are often used. We evaluated the current databases regarding FBN1 variants and validated associated phenotype records with a new Marfan syndrome geno-phenotyping tool called the Marfan score.
  
  
  
  We evaluated four databases (UMD-FBN1, ClinVar, the Human Gene Mutation Database (HGMD), and Uniprot) containing 2,250 FBN1 variants supported by 4,904 records presented in 307 references. The Marfan score calculated for phenotype data from the records quantified variant associations with Marfan syndrome phenotype. We calculated a Marfan score for 1,283 variants, of which we confirmed the database diagnosis of Marfan syndrome in 77.1%. This represented only 35.8% of the total registered variants; 18.5-33.3% (UMD-FBN1 versus HGMD) of variants associated with Marfan syndrome in the databases could not be confirmed by the recorded phenotype.
  
  
  
  FBN1 databases can be imprecise and incomplete. Data should be used with caution when evaluating FBN1 variants. At present, the UMD-FBN1 database seems to be the biggest and best curated; therefore, it is the most comprehensive database. However, the need for better genotype-phenotype curated databases is evident, and we hereby present such a database.Genet Med advance online publication 01 December 2016.
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.|Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Kristian A
authors.identifier: 0000-0002-3452-8298
authors.initials: KA
authors.lastname: Groth
authors.affiliation: German Aorta Centre of Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Yskert
authors.initials: Y
authors.lastname: Von Kodolitsch
authors.affiliation: Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Kutsche
authors.affiliation: Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Mette
authors.initials: M
authors.lastname: Gaustadnes
authors.affiliation: Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Kasper
authors.identifier: 0000-0003-0195-4685
authors.initials: K
authors.lastname: Thorsen
authors.affiliation: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Niels H
authors.initials: NH
authors.lastname: Andersen
authors.affiliation: Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.|Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Claus H
authors.initials: CH
authors.lastname: Gravholt
mesh_terms: D016208:Databases, Factual; D030561:Databases, Nucleic Acid / Q000592:standards; D005260:Female; D000071838:Fibrillin-1 / Q000235:genetics*; D000071837:Fibrillins; D056726:Genetic Association Studies / Q000379:methods*; D005820:Genetic Testing / Q000379:methods; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D008297:Male; D008382:Marfan Syndrome / Q000175:diagnosis* / Q000235:genetics; D008840:Microfilament Proteins / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605722:FBN1 protein, human; D054392:Adipokines