UW ISeqU: Clinical Impact of Whole-genome Sequencing in Adults

This is a prospective observational cohort study evaluating the use of clinical whole genome sequencing in adults with unexplained medical conditions, atypical disease courses, or clinical presentations for which a genetic contribution is suspected. Participants will be identified at the University of Washington Medicine sites (UW Montlake and Harborview Medical Center). The study is intended to characterize how genome sequencing can be incorporated into adult clinical care. Participation is voluntary and does not replace standard diagnostic evaluation or treatment.

Potential participants will be identified through review of hospital admissions and referrals from treating clinicians or specialty services. Informed consent may be completed in person, by telephone, or by secure videoconference. When a hospitalized participant is unable to provide consent because of illness or impaired decision-making capacity, consent may be obtained from a legally authorized representative in accordance with applicable requirements. During consent, participants will indicate whether they wish to receive ACMG medically actionable secondary findings and whether they agree to future contact.

After enrollment, the study team will collect clinical and phenotypic information relevant to genomic interpretation. Information may include the participant's presenting symptoms, medical and family history, prior diagnostic testing, medications, hospital course, and subsequent clinical care. Data will be obtained from participant or family interview, review of the electronic health record, and communication with the treating team. Clinical information from before and after sequencing will be collected to support interpretation and to evaluate the downstream effects of genomic findings.

The only physical procedure is collection of a biospecimen for genomic testing. Research blood collection will be coordinated with a clinically indicated blood draw to avoid an additional venipuncture. Alternatively, a buccal swab may be used.

A close biological relative may also be enrolled as a genetic comparator when this would assist in genetic interpretation. Comparator participation is optional. Comparators will provide a buccal specimen and limited identifying information needed for laboratory testing. Their medical records will not be reviewed.