Using variants at LOD for NGS PT is a crucial aspect of ensuring the accuracy and reliability of NGS assays because it allows participating laboratories to assess the sensitivity of their NGS LDT by challenging them to identify variants present at low allelic fractions. Because clinical samples are frequently small and contain variants at low allelic frequencies, testing against PT samples with low VAF helps laboratories identify potential issues with sensitivity, assay performance, and data analysis, allowing for the improvement of processes and procedures. Because a major goal of the SPOT/Dx pilot study was to determine the performance of NGS LDTs, it was designed to include challenging variants with low VAF, similar to CAP PT programs.5 However, the design of the SPOT/Dx pilot study differed from conventional PT programs in several ways, and as a result its conclusions represent an underestimation of the actual performance of the participating laboratories.4 For example, the reference materials in the SPOT/Dx pilot were designed with VAFs hovering near the LOD of NGS LDTs used by most of the participating laboratories. ...the performance of NGS LDTs was underestimated, leading to erroneous impressions regarding the quality and accuracy of these LDTs. Laboratories frequently encounter situations where they must analyze new or emerging substances, employ customized testing methods, or cater to specific patient groups not covered by existing PT programs. ...the introduction of innovative technologies and testing approaches may not always align with the availability