Minigene Splice Assays Allow Pathogenicity Reclassification of <i>RPE65</i> Variants of Uncertain Significance.

ABSTRACT:

Background/objectives

Obtaining a genetic diagnosis for patients with inherited retinal diseases has become even more important since gene-specific therapies have become available. When genetic screening reveals variants of uncertain significance (VUS), additional evidence is required to determine genetic eligibility for therapy. Confirming the effect on splicing that is predicted by SpliceAI could change their classification to either likely pathogenic or pathogenic and would therefore be of great importance when interpreting these variants when geneticists worldwide are trying to reach a diagnosis.

Methods

Using minigene assays, we established a pipeline to assess the effect on splicing for all variants. We selected 73 RPE65 variants that were classified as either V

SUBMITTER: Panneman DM 

PROVIDER: S-EPMC12469365 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature