EPAS1 and polycythemia: Our study has several weaknesses: we had very limited clinical information from most subjects, and were not able to examine whether these EPAS1 variants were associated with more aggressive disease or (other than case #3) with polycythemia; statistical comparison with gnomAD controls is limited by the very low MAF for each variant in our cases and we only used transient transfections for our functional studies, which may have missed more subtle effects on transcriptional induction by some variants and/or effects on cell proliferation.