title: The pathogenicity of genetic variants previously associated with left ventricular non-compaction.
abstract: BACKGROUND
  Left ventricular non-compaction (LVNC) is a rare cardiomyopathy. Many genetic variants have been associated with LVNC. However, the number of the previous LVNC-associated variants that are common in the background population remains unknown. The aim of this study was to provide an updated list of previously reported LVNC-associated variants with biologic description and investigate the prevalence of LVNC variants in healthy general population to find false-positive LVNC-associated variants.
  
  
  RESULTS
  The Human Gene Mutation Database and PubMed were systematically searched to identify all previously reported LVNC-associated variants. Thereafter, the Exome Sequencing Project (ESP) and the Exome Aggregation Consortium (ExAC), that both represent the background population, was searched for all variants. Four in silico prediction tools were assessed to determine the functional effects of these variants. The prediction results of those identified in the ESP and ExAC and those not identified in the ESP and ExAC were compared. In 12 genes, 60 LVNC-associated missense/nonsense variants were identified. MYH7 was the predominant gene, encompassing 24 of the 60 LVNC-associated variants. The ESP only harbored nine and ExAC harbored 18 of the 60 LVNC-associated variants. In total, eight out of nine ESP-positive variants overlapped with the 18 variants identified in ExAC database.
  
  
  CONCLUSIONS
  In this article, we identified 9 ESP-positive and 18 ExAC-positive variants of 60 previously reported LVNC-associated variants, suggesting that these variants are not necessarily the monogenic cause of LVNC.
authors.affiliation: The Danish National Research Foundation Center for Cardiac Arrhythmia (DARC)CopenhagenDenmark; Laboratory of Molecular CardiologyDepartment of CardiologyThe Heart CentreCopenhagen University Hospital RigshospitaletCopenhagenDenmark; Department of CardiologyThe Heart CenterRigshospitaletCopenhagenDenmark.
authors.forename: Yeganeh
authors.initials: Y
authors.lastname: Abbasi
authors.affiliation: The Danish National Research Foundation Center for Cardiac Arrhythmia (DARC)CopenhagenDenmark; Laboratory of Molecular CardiologyDepartment of CardiologyThe Heart CentreCopenhagen University Hospital RigshospitaletCopenhagenDenmark; Department of CardiologyThe Heart CenterRigshospitaletCopenhagenDenmark.
authors.forename: Javad
authors.initials: J
authors.lastname: Jabbari
authors.affiliation: The Danish National Research Foundation Center for Cardiac Arrhythmia (DARC)CopenhagenDenmark; Laboratory of Molecular CardiologyDepartment of CardiologyThe Heart CentreCopenhagen University Hospital RigshospitaletCopenhagenDenmark; Department of CardiologyThe Heart CenterRigshospitaletCopenhagenDenmark.
authors.forename: Reza
authors.initials: R
authors.lastname: Jabbari
authors.affiliation: The Danish National Research Foundation Center for Cardiac Arrhythmia (DARC)CopenhagenDenmark; Laboratory of Molecular CardiologyDepartment of CardiologyThe Heart CentreCopenhagen University Hospital RigshospitaletCopenhagenDenmark; Department of CardiologyInstitute of Cardiovascular DiseaseThe Heart CenterThe Second Affiliated HospitalNanchang UniversityNanchangChina.
authors.forename: Ren-Qiang
authors.initials: RQ
authors.lastname: Yang
authors.affiliation: The Danish National Research Foundation Center for Cardiac Arrhythmia (DARC)CopenhagenDenmark; Laboratory of Molecular CardiologyDepartment of CardiologyThe Heart CentreCopenhagen University Hospital RigshospitaletCopenhagenDenmark; Department of CardiologyThe Heart CenterRigshospitaletCopenhagenDenmark.
authors.forename: Bjarke
authors.initials: B
authors.lastname: Risgaard
authors.affiliation: Department of CardiologyThe Heart CenterRigshospitaletCopenhagenDenmark; Department of Clinical MedicineFaculty of Health and Medical ScienceUniversity of CopenhagenCopenhagenDenmark.
authors.forename: Lars
authors.initials: L
authors.lastname: Køber
authors.affiliation: The Danish National Research Foundation Center for Cardiac Arrhythmia (DARC)CopenhagenDenmark; Laboratory of Molecular CardiologyDepartment of CardiologyThe Heart CentreCopenhagen University Hospital RigshospitaletCopenhagenDenmark; Department of CardiologyThe Heart CenterRigshospitaletCopenhagenDenmark; Department of Clinical MedicineFaculty of Health and Medical ScienceUniversity of CopenhagenCopenhagenDenmark.
authors.forename: Stig
authors.initials: S
authors.lastname: Haunsø
authors.affiliation: The Danish National Research Foundation Center for Cardiac Arrhythmia (DARC)CopenhagenDenmark; Laboratory of Molecular CardiologyDepartment of CardiologyThe Heart CentreCopenhagen University Hospital RigshospitaletCopenhagenDenmark; Department of CardiologyThe Heart CenterRigshospitaletCopenhagenDenmark; Department of Clinical MedicineFaculty of Health and Medical ScienceUniversity of CopenhagenCopenhagenDenmark.
authors.forename: Jacob
authors.initials: J
authors.lastname: Tfelt-Hansen
keywords: Exome aggregation consortium; Exome sequencing project; LVNC; LVNC‐associated variants; genes; human gene mutation database; left ventricular non‐compaction; variants