Integrative Genomic Mapping and Visualization From Curated Public Datasets Reveals Germline RB1 Variant Diversity in Retinoblastoma.

Germline RB1 variants (mostly truncating); bilateral disease predominates among germline cases.

Consolidation of 3004 retinoblastoma RB1 variants (1943 germline, 797 somatic) from the Leiden Open Variation Database, 13 published cohorts and COSMIC, reannotated in HGVS nomenclature and mapped to GRCh38. Germline truncating variants account for more than 80 % of variants and missense for 9.2 %, with highest density in exons 4 and 15. Among germline cases with known laterality, 81.2 % were bilateral, and only 39.4 % of germline variants were reported in ClinVar. The PANORAMA tool enables interactive visualisation and filtering of aggregated or user-uploaded variants.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The main value is bringing a scattered RB1 landscape into a unified, HGVS/GRCh38-standardised resource — valuable when fewer than 40 % of germline variants are in ClinVar. Useful for interpretation and counselling in hereditary retinoblastoma, though the contribution remains that of a consolidation tool rather than a direct clinical advance.

Analysis by Dr Thibaut Benquey