To determine whether any of these variations had been described previously, we consulted the publically available data on the NHLBI Exome Sequencing Project Exome Variant Server (EVS). Of the mutations reported in this study, only one (c.1548G>T, reported at a frequency of 1/12,937 on the NHLBI EVS, accessed December 2012) had been reported on this website in over 12,000 exomes sequenced. We also had access to the exome data from an additional 60 individuals, and none of the variations reported here were seen in this group. Using the same filtering criteria (absent in the 1000 Genomes data set), we found the combined frequency of rare RTEL1 nonsynonymous, loss-of-function, and splice variants in the NHLBI data set to be between 2.3% in European Americans and 3.4% in African Americans. Hence, the expected frequency of individuals carrying biallelic RTEL1 variants was much lower in the control population (approximately 1/1,000) than in our disease group (6/23, chi-square p < 10−10). On the basis of this, we suggest that these mutations are causal for disease in a subset of individuals with HHS.