Diagnostic Genome Sequencing

The diagnostic pipeline produced positive genetic diagnoses in 24.8% of probands. Most diagnosed probands had potential changes in clinical management after genome sequencing. Genome sequencing shortened a long diagnostic odyssey among positively diagnosed probands. Richer phenotyping was associated with improved diagnostic yield. Family-based sequencing had a higher diagnostic yield than singleton sequencing. A substantial share of pathogenic or likely pathogenic SNVs and indels were novel.