Although new molecular technologies and computational prediction tools offer wide-raging opportunities in genetic diagnostic settings, they have many limitations. We contextualize these limitations by investigating incorrect variant detection in genomic regions of high sequence similarities and from inappropriate computational analysis. For instance, we observed a 5% false positive rate in MYH7 variant detection due to high sequence similarity to MYH6. Additionally, using inappropriate computational files during analysis (eg. annotation and default files) significantly increased the risk of incorrect variant detection for certain genes. This study shows that molecular technologies have limitations that need to be addressed to avoid inaccurate diagnoses. (By Dr. Landry Nfonsam, https://jmg.bmj.com/content/early/2018/09/21/jmedgenet-2018-105443 )