RIT1 and Noonan syndrome: For instance the c.650C>G p.(Ser217*) variant in the RIT1 gene, associated with Noonan syndrome 8 (MIM #615355), may be classified as pathogenic if PVS1 is used at a very strong level (Figure 1A); however, more detailed evaluation according to the guidelines provided by Abou Tayoun et al. [10] through the AutoPVS1 algorithm suggests using the criterion at moderate level (see Figure 2), thus leading to an uncertain significance interpretation (Figure 1B).