We used the oligonucleotide-directed mutagenesis screen to investigate the phenotype of 18 MSH6 VUS described in literature and the InSiGHT database as well as 8 MSH6 VUS detected in suspected-LS patients from the Erasmus Medical Center Rotterdam and the Radboud University Medical Center Nijmegen (see S1 and S2 Tables for clinical data [27–38]; see S3 Fig for location of variants in MSH6 [39,40]). The gene discussed is MSH6; the disease is Leigh syndrome.