Variants of uncertain significance: At the crux of diagnostic odyssey

The variants of uncertain significance (VUS) have caught an immense interest ever since the next-generation sequencing (NGS) capture technologies spanned beyond the vast majority of inferring disease-causing mutations. On the other hand, as genetic variation is best seen in non-coding regions, interpreting the mutations at exon-intron boundaries with large numbers of VUS has gained significance. This allows VUS more interesting and augurs well for pathogenicity even as non-synonymous mutations effectively are to be included among those swaths of genomic variant pool. In this perspective, we provide how VUSs serve as an interface and crux of the diagnostic odyssey.