Zawar Akshaykumar, Manoj Gautham, Nair Pramod P, Deshpande Poonam, Suravajhala Renuka, Suravajhala Prashanth
Bioclues.org, Hyderabad, India; Department of Life Sciences, School of Science and Mathematics, DES Pune University, Pune, Maharashtra 411004, India; GeneSpectrum Life Sciences LLP, Office No. 304, R Square, Warje, Pune, Maharashtra 411058, India.
Faculty of Interdisciplinary Studies, Amrita Vishwa Vidyapeetham, Clappana PO 690525, Kerala, India.
Gene. 2025 Aug 20;962:149587. doi: 10.1016/j.gene.2025.149587. Epub 2025 May 20.
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.
自从下一代测序（NGS）捕获技术超越了绝大多数推断致病突变的范围以来，意义未明的变异（VUS）就引起了极大的关注。另一方面，由于遗传变异在非编码区域最为常见，解读具有大量VUS的外显子-内含子边界处的突变变得至关重要。这使得VUS更具吸引力，即使非同义突变实际上被纳入基因组变异库的众多部分中，也预示着其具有致病性。从这个角度来看，我们阐述了VUS如何作为诊断过程的一个界面和关键所在。
