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