Table 2 |.

Overview of molecular variants identified in UDN318336 via multi-ome long-read sequencing

Molecular event	‘ome(s) required for identification	Associated clinical phenotype	Proposed mechanism	Overlapping Mendelian condition
NBEA haploinsufficiency	Genome	Developmental delay	NBEA nonsense-mediated decay on der(13)	MIM 619157
PDK3-MAB21L1 fusion kinase transcript	Transcriptome	Polymicrogyria, sensorineural hearing loss, developmental delay, lactic acidosis, and hypotonia.	Overexpression of PDK3 in tissue that endogenously expresses MAB21L1. Potentially altered regulation of PDK3-MAB21L1 fusion protein product.	MIM 300905; MIM 312170
PDK3 adoption of MAB21L1 enhancer and subsequent PDK3 ectopic gain-of-expression	Chromatin epigenome
X chromosome inactivation of RB1 locus	Chromatin epigenome	Bilateral retinoblastomas	‘First hit’ in development of biallelic RB1 LOF	MIM 180200
Transcriptional readthrough silencing of MAB21L1	CpG methylome; Chromatin epigenome; Transcriptome	No impact on patient phenotype as only one MAB21L1 haplotype impacted, with other haplotype demonstrating intact gene regulation.	N/A	MIM 618479