ClinGen and Genetic Testing

To the Editor: Easton et al. (June 4 issue) 1 highlight the challenges that genomic laboratories face when classifying rare variants. Predictions of cancer risk are typically extrapolated from burden tests, under the assumption of equal pathogenicity for every variant, which may not always be accurate. For example, CDH1 C-terminal truncating variants are predicted to retain partial function, and therefore cancer risk associated with these variants should be evaluated carefully. 2 , 3 The authors argue that although it would be ideal to have specific evidence for every variant, most are rare, making the task “infeasible.” 1 Although it is difficult to collect enough . . .