Danny E. Miller from the University of Washington presented at London Calling 2025 on “A diagnostic blind spot: an intronic SVA_E insertion as the most common cause of Canavan disease.” Miller returned to some ideas he has presented saying long-read sequencing has great potential for genetic workups. Traditional genetic workup is often “stepwise and diagnostic in less than 50% of cases,” said Miller. With several clinical examples, Miller, shared how long-read sequencing can identify variants often missed by prior clinical testing. For example, an individual with a glycogen storage disease was resolved with phasing of the entire gene variant. Canavan disease cases were also studied in collaboration with another lab. For eight cases, they sequenced and detected an insertion of a transposable element. Long-read sequencing and RNA sequencing can help identify the most common pathogenic variants. Miller and team have created a tools to filter and analyze structural variants from data from the 1000 Genomes Project. The needLR is another tool developed by the lab to use long-reads for annotating variants. Miller predicts long-read sequencing will become a common tool in clinical testing.
