Table 1.

Examples for the specific ERN cohorts and the unsolvables.

Cohort	Rationale
Cohort 2: Long-read whole genome sequencing (LR-WGS)
X-linked spinal and bulbar muscular atrophy (SBMA)	Suspected expansions of repeat disorder or other hidden structural variants (SV)
Hereditary ataxia	Suspected expansions of repeat disorder or other hidden SVs
Cohort 2: Genomics and Epigenomics
Unexplained Intellectual Disability (ID): patient-parent trios	De novo mutation prioritisation very powerful filter for de novo methylation changes
Diffuse gastric cancer	Hypermethylation of cancer gene promoter known disease mechanism
Rare pheochromocytomas and paragangliomas	Hypermethylation of cancer gene promoter known disease mechanism
Cohort 4
Unsolved syndromes available via ERN ITHACA	Aicardi syndrome, Gomez–Lopez Hernandes syndrome, Hallermann–Streiff syndrome are clinically well-defined entities and have been studied by WES and WGS globally and remain unsolved