Fig. 4

The novel missense variant p.Cys3251Tyr affects a conserved amino acid and predicted to be pathogenic. A. Sequence conservation of p.Cys3251 in orthologous USH2A protein sequences aligned using ClustalOmega. Cys3251, shown in blue, is completely conserved (*) throughout mammals, birds and fish. B. Comparison of VEP scores for 3239 putatively benign missense variants observed in the human population, taken from gnomAD v2.0, and 102 pathogenic and likely pathogenic missense variants from ClinVar. The top-five performing VEPs are included here, and the performance of all 32 tested predictors is summarized in Supplementary Table 1. The predictions for the novel p.Cys3251Tyr mutation is shown in red, and clearly clusters with the known pathogenic variants for all predictors