We believe that the report of the yield and interpretability of clinical whole-genome sequencing by Dr Dewey and colleagues1 is unduly pessimistic about the present and future efficacy of this molecular genetic technology in clinical medicine. Their experience of low coverage of key disease genes, poor nucleotide-calling reproducibility, low diagnostic yield, and insurmountable interpretative challenges for unexpected variants is at odds with that of most centers offering clinical genomic sequencing,2 including our own.