Could genome sequencing be used to prospectively identify people at high risk for having a genetic disorder? And, could this enable early multidisciplinary care and avoid life-threatening events? On this month’s GenePod, Bruce D. Gelb, MD, director of the Mindich Child Health and Development Institute at Mount Sinai’s Icahn School of Medicine, describes the genotype-first approach his team took. Dr. Gelb and his team used biobanks to identify individuals with variants likely causing heart conditions associated with RASopathies or Marfan syndrome. The team then went to the electronic health records of those individuals to determine if they had been diagnosed; many had not! Furthermore, identifying individuals by genotype first yielded new insights into their phenotypes.