2026-05-22T18:20:50Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/157602024-09-27T08:15:32Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc Pozo, Fernando author Rodriguez, Jose Manuel author Vazquez, Jesus author Tress, Michael L author 2022-10-18 Clinical variant interpretation is highly dependent on the choice of reference transcript. Although the longest transcript has traditionally been chosen as the reference, APPRIS principal and MANE Select transcripts, biologically supported reference sequences, are now available. In this study, we show that MANE Select and APPRIS principal transcripts are the best reference transcripts for clinical variation. APPRIS principal and MANE Select transcripts capture almost all ClinVar pathogenic variants, and they are particularly powerful over the 94% of coding genes in which they agree. We find that a vanishingly small number of ClinVar pathogenic variants affect alternative protein products. Alternative isoforms that are likely to be clinically relevant can be predicted using TRIFID scores, the highest scoring alternative transcripts are almost 700 times more likely to house pathogenic variants. We believe that APPRIS, MANE and TRIFID are essential tools for clinical variant interpretation. NPJ Genom Med. 2022 Oct 18;7(1):59 10.1038/s41525-022-00329-6 2056-7944 NPJ genomic medicine 36257961 http://hdl.handle.net/20.500.12105/15760 Clinical variant interpretation and biologically relevant reference transcripts.