Phenotypic variations in carriers of predicted protein-truncating genetic variants in MYBPC3: an autopsy-based case series

Nori Williams, Robert W. Marion, Thomas V. McDonald, Dawei Wang, Bo Zhou, Lucy S. Eng, Sung Yon Um, Ying Lin, Kevin Ruiter, Lisa Rojas, Barbara A. Sampson, Yingying Tang

Research output: Contribution to journalArticle

3 Scopus citations


Our aim is to characterize predicted protein-truncating variants (PTVs) in MYBPC3, the gene most commonly associated with hypertrophic cardiomyopathy (HCM), found in a series of autopsied HCM cases after sudden unexpected cardiac death. All cases underwent death scene investigation, gross and microscopic autopsies, toxicological testing, a review of medical records, and a molecular analysis of 95 cardiac genes. We found four pathogenic PTVs in MYBPC3 among male decedents. All variants were previously submitted to ClinVar without phenotype details. Two PTVs were located in the cardiac-specific myosin S2-binding (M) motif at the N-terminus of the MYBPC3-encoded cMyBP-C protein, and two PTVs were in the non-cardiac-specific C-terminus of the protein. The carriers of two cardiac-specific M-motif PTVs died at age 38 years; their heart weight (HW, g) and body mass index (BMI, kg/m2) ratio were 34.90 (890/25.5) and 23.56 (980/41.6), respectively. In contrast, the carriers of two non-cardiac-specific C-terminal PTVs died at age 57 and 67 years, respectively; their HW and BMI ratio were 14.71 (450/30.6) and 13.98 (600/42.9), respectively. A detailed three-generation family study was conducted in one case. This study showed age-at-death variations among MYBPC3 PTVs carriers in adult males.

Original languageEnglish (US)
Pages (from-to)30-33
Number of pages4
JournalCardiovascular Pathology
Publication statusPublished - Nov 1 2018



  • Hypertrophic cardiomyopathy
  • MYBPC3
  • Sudden death
  • Truncating variants

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Cardiology and Cardiovascular Medicine

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