Table 7 Goals of each step of a UDP, and key aspects of each

Enrolment

Equitable access to the UDP

• Broad recruitment from a range of clinical services

• Inclusion of individuals involved in past non-diagnostic research

• Clear inclusion/exclusion criteria, enabling individuals and clinicians to understand pathways to eligibility

Phenotyping

Comprehensive understanding of individual phenotype

• Re-phenotyping within the program, ideally with a multidisciplinary team

Research diagnostics

Extensive analysis of the affected individual’s genome and functional impact of detected variants of uncertain significance

• Use of unbiased genomic sequencing (ES or WGS)

• Access to novel technologies (e.g., long read sequencing) and multiomics (e.g., RNA sequencing)

• Pathway to functional studies as required to clarify pathogenicity of novel and uncertain findings

• Periodic reanalysis of undiagnosed individuals

Data sharing and matchmaking

Data-sharing to optimize chance of diagnosis

• Sharing to MME, UDNI or other diagnostic networks as part of diagnostic pipeline

Results and follow-up

Clear procedure for return of results to individual

• Genetic counsellor involvement in return of results

• Discussion of individual experience in UDP