In this particular case, the fact that two studies reported the same recurrent MITF mutation in independent patient series/populations using an agnostic genome-wide approach (massive parallel exome sequencing approach plus genotyping in larger melanoma series, familial CMM, where multiple primaries often occur) reinforces the notion of the existence of variants with low minor allele frequency that could have substantial effects (Figure 2). This evidence concerns the gene MITF and melanoma.