To address the challenges of HRD detection and therapy, we propose a refined conceptual model integrating genomic (e.g., Myriad myChoice CDx, FoundationOne CDx, Caris HRD), functional (e.g., RAD51 foci, DNA fiber assay), epigenetic (e.g., BRCA1/RAD51C methylation) assays and epitranscriptomic RNA modifications/methylation (e.g., to capture the full HRD spectrum, including non-BRCA defects. This evidence concerns the gene RAD51C and hypoparathyroidism-retardation-dysmorphism syndrome.