The trap of genetic tag: The importance of pathogenicity prediction tools in the correct interpretation of variants of uncertain significance in the era of high‐throughput genome sequencing

Abstract

AbstractAlthough recent advancements in DNA sequencing technologies and their widely used, the interpretation of variants of uncertain significance from these large datasets is not clear‐cut. Here, we present the case of a family referred to our metabolic disease department, in which three males' individuals were affected by a suspected a genetic inherited disease, resulting from next‐generation sequencing results. A correct assessment of the clinical significance of the genetic variant found in our cases, with a review of the literature, the evaluation of population database and the use of computational predictive program changed the initial suspect. Despite NGS technologies have increased diagnostic sensitivity, most of these variants remains of uncertain clinical significance. An efficient systematic approach is fundamental to determine the pathogenicity of a variant, avoiding incorrect interpretation in a clinical setting.