dc.contributor.author | Pozo, Fernando | |
dc.contributor.author | Rodriguez, Jose Manuel | |
dc.contributor.author | Vazquez, Jesus | |
dc.contributor.author | Tress, Michael L | |
dc.date.accessioned | 2023-04-11T13:45:45Z | |
dc.date.available | 2023-04-11T13:45:45Z | |
dc.date.issued | 2022-10-18 | |
dc.identifier.citation | NPJ Genom Med. 2022 Oct 18;7(1):59 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/15760 | |
dc.description.abstract | 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. | es_ES |
dc.description.sponsorship | Research reported in this publication was supported by the National Human Genome
Research Institute of the National Institutes of Health under Award Number
U24HG007234. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Research was also supported by the following grants: PGC2018-097019-B-I00/Ministry of Science,
Innovation and Universities; IPT17/0019/Carlos III Institute of Health-Fondo de Investigación Sanitaria; HR17-00247/'la Caixa' Foundation. We would like to thank the referees for their constructive suggestions. We believe they have improved the paper considerably. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Nature Publishing Group | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.title | Clinical variant interpretation and biologically relevant reference transcripts. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 36257961 | es_ES |
dc.format.volume | 7 | es_ES |
dc.format.number | 1 | es_ES |
dc.format.page | 59 | es_ES |
dc.identifier.doi | 10.1038/s41525-022-00329-6 | es_ES |
dc.contributor.funder | National Institutes of Health (Estados Unidos) | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.contributor.funder | Fundación La Caixa | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2056-7944 | es_ES |
dc.relation.publisherversion | 10.1038/s41525-022-00329-6 | es_ES |
dc.identifier.journal | NPJ genomic medicine | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Proteómica cardiovascular | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PGC2018-097019-B-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/IPT17/0019 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/HR17-00247 | es_ES |