Monogenic Risk

  • Monogenic (Mendelian) conditions are caused by pathogenic variants in a single gene.
  • These pathogenic variants are rare and have high penetrance, and thus have a large impact on the risk of developing a condition.
  • For example, a pathogenic variant in the BRCA1 gene increases a woman's lifetime risk of developing breast cancer to more than 50% if there is no medical intervention.
  • If the monogenic condition has an autosomal dominant pattern of inheritance, a single variant is enough to cause the condition, and an individual has a 50% chance of passing the monogenic variant to a child.
  • Monogenic risk is what has classically been tested in genetics, but monogenic diseases are relatively uncommon.
  • Children in this study are not tested for monogenic risks and the monogenic results are returned only to adults.
  • Sequencing for pathogenic variants will be performed in 16 genes: BRCA1, BRCA2, MLH1, MSH2, MSH6, PMS2, EPCAM, APOB, LDLR, LDLRAP1, PCSK9, PALB2, PTEN, STK11, TP53, LMNA.
  • Monogenic results will be returned for the following conditions:
    • Atrial Fibrillation
    • Breast Cancer
    • Colorectal Cancer
    • Coronary Heart Disease
    • Hypercholesterolemia
    • Prostate Cancer