title: Large gene panel sequencing in clinical diagnostics-results from 501 consecutive cases.
abstract: BACKGROUND
  In addition to whole exomes, large gene panels of clinically associated genes are used as high-throughput sequencing tests in many clinical centers, but their clinical utility has been much less investigated.
  
  
  METHODS
  Here we report the results of the 501 first unselected cases for whom TruSight One panel (Illumina Inc., San Diego, California) was sequenced as a clinical diagnostic test for a variety of indications in our department. The analysis was restricted to virtual subpanels based on referral forms, where doctors were asked to list candidate genes or select one from predefined larger panels.
  
  
  RESULTS
  A probable or definite pathogenic finding was reported in 26.3% of cases. In 238 samples for whom 1 to 9 genes were requested for analysis, the diagnostic yield was significantly higher compared to other 263 cases for whom larger subpanels were requested (31.5% vs 21.7%, respectively, P = .016). Detected mutations included single nucleotide variants, small insertions and deletions, and larger copy number variants. Out of 157 reported mutations, 67 were previously undescribed.
  
  
  CONCLUSIONS
  The clinical utility of large gene panel sequencing in the context of other genetic diagnostic tests is discussed in detail.
authors.affiliation: Department of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.|Department of Clinical Genetics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
authors.forename: S
authors.identifier: http://orcid.org/0000-0002-5435-0781
authors.initials: S
authors.lastname: Pajusalu
authors.affiliation: Department of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.|Department of Clinical Genetics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
authors.forename: T
authors.initials: T
authors.lastname: Kahre
authors.affiliation: Department of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.
authors.forename: H
authors.initials: H
authors.lastname: Roomere
authors.affiliation: Department of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.
authors.forename: Ü
authors.initials: Ü
authors.lastname: Murumets
authors.affiliation: Department of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.
authors.forename: L
authors.initials: L
authors.lastname: Roht
authors.affiliation: Department of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.
authors.forename: K
authors.initials: K
authors.lastname: Simenson
authors.affiliation: Department of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.|Department of Clinical Genetics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.|Department of Biomedicine, Institute of Biomedicine and Translational Medicine, University of Tartu, Tartu, Estonia.
authors.forename: T
authors.initials: T
authors.lastname: Reimand
authors.affiliation: Department of Clinical Genetics, United Laboratories, Tartu University Hospital, Tartu, Estonia.|Department of Clinical Genetics, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
authors.forename: K
authors.initials: K
authors.lastname: Õunap
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D056915:DNA Copy Number Variations; D059472:Exome / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation; D055815:Young Adult
keywords: 
  DNA copy number variations; clinical genetic diagnostics; high-throughput nucleotide sequencing; large gene panel sequencing; whole exome sequencing