In the current study, we aimed to validate and further delineate the effect of NOTCH3  PV position on CADASIL disease variability, by analysing the correlation between PV position and brain MRI lesion load, age at first stroke and survival in two independent large CADASIL samples.4 Furthermore, we compared the locations of NOTCH3 PV in European CADASIL patients with those in the general European population, using the  genome  Aggregation Database (gnomAD). The gene discussed is NOTCH3; the disease is stroke disorder.