Molecular genetic approaches have evolved at an astonishing pace resulting in increasingly routine use of whole exome sequencing in Mendelian disorder diagnosis. After whole exome sequencing, 50% to 75% of patients remain without a genetic diagnosis, indicating limitations in variant calling and prioritization and a role for noncoding variants. Whole genome sequencing has the potential to reveal all genetic variants; however, it escalates the challenge of variant prioritization owing to the vast numbers called. Promising approaches to aid in variant interpretation include the integration of functional genomic data such as transcriptome sequencing, which achieves diagnostic yields of 10% to 35%. International-scale collaboration and establishment of data repositories are paramount in accelerating the diagnosis of Mendelian disorders.     «

Molecular genetic approaches have evolved at an astonishing pace resulting in increasingly routine use of whole exome sequencing in Mendelian disorder diagnosis. After whole exome sequencing, 50% to 75% of patients remain without a genetic diagnosis, indicating limitations in variant calling and prioritization and a role for noncoding variants. Whole genome sequencing has the potential to reveal all genetic variants; however, it escalates the challenge of variant prioritization owing to the vas...     »