title: Clinical genetic testing in pediatric cardiomyopathy: Is bigger better?
abstract: BACKGROUND
  For clinical genetic testing of cardiomyopathy (CMP), current guidelines do not address which gene panels to use: targeted panels specific to a CMP phenotype or expanded (panCMP) panels that include genes associated with multiple phenotypic subtypes.
  
  
  OBJECTIVE
  Our objective was to assess the clinical utility of targeted versus panCMP panel testing in pediatric CMPs.
  
  
  METHODS
  151 pediatric patients with primary hypertrophic (n = 66), dilated (n = 64), restrictive (n = 8), or left-ventricular non-compaction (n = 13) CMP who underwent clinical genetic panel testing at a single centre were included. PanCMP (n = 47) and targeted panel testing (n = 104) were compared for yield of pathogenic variants and variants of unknown significance (VUS).
  
  
  RESULTS
  Pathogenic variants were identified in 26% of patients, 42% had indeterminate results (only VUS detected), and 32% had negative results. Yield was lower (15%) in panCMP vs. targeted panel testing (32%) (P = .03) in all CMP subtypes. VUS detection was higher with panCMP (87%) than targeted panel testing (30%) (P <.0001). PanCMP panel testing only identified pathogenic variants in genes that overlapped targeted panels.
  
  
  CONCLUSIONS
  PanCMP testing did not increase diagnostic yield compared to targeted panel testing. Until accuracy of variant interpretation with panCMP panels improves, targeted panels may be suitable for clinical testing in pediatric CMP.
authors.affiliation: Division of Cardiology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: A C
authors.identifier: http://orcid.org/0000-0002-1846-2612
authors.initials: AC
authors.lastname: Ouellette
authors.affiliation: Cardiology Department, The Royal Children's Hospital, Melbourne, Victoria, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Mathew
authors.affiliation: Division of Cardiology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: A K
authors.initials: AK
authors.lastname: Manickaraj
authors.affiliation: Division of Cardiology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Manase
authors.affiliation: Division of Cardiology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Zahavich
authors.affiliation: Division of Cardiology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Wilson
authors.affiliation: Division of Cardiology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: K
authors.initials: K
authors.lastname: George
authors.affiliation: Division of Cardiology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Benson
authors.affiliation: Division of Cardiology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Bowdin
authors.affiliation: Division of Cardiology, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Mital
mesh_terms: D009202:Cardiomyopathies / Q000175:diagnosis / Q000235:genetics*; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000379:methods*; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D008297:Male; D009154:Mutation; D015203:Reproducibility of Results; D012189:Retrospective Studies
keywords: cardiology; cardiomyopathy; genetics; pediatrics