Response to Shah et al: Using high-resolution variant frequencies empowers clinical genome interpretation and enables investigation of genetic architecture
Main text Main text Supplemental Data description Declaration of Interests Web Resources References Recent work by Shah and colleagues1 demonstrated that many variants in the ClinVar database2 are misclassified, and that disease-specific allele frequency (AF) thresholds can identify wrongly classified alleles by flagging variants that are too prevalent in the population to be causative of rare penetrant disease. While we agree with the main conclusions of this work, the authors compare their AF filtering approach to our recently published method3, concluding that the method we advanced \"may be prone to removing potentially pathogenic variants\". This is incorrect. Here we demonstrate that our approach is robust, and further illustrate the power of di ...