It has recently been shown that NOTCH3 EGFr 1 to 6 pathogenic variants may cause a more severe phenotype with earlier age at stroke onset, lower survival time, and greater brain MRI lesions when compared with EGFr 7 to 34 pathogenic variants.[12,13] However, the genotype-phenotype association has not been firmly established. This evidence concerns the gene NOTCH3 and Stroke.