Protein-truncating variants explained

Protein-truncating variants (PTVs) are genetic variants predicted to shorten the coding sequence of genes,^[1] through ways like a stop-gain mutation.^{[2] [3] [4] [5]} PTV is sometime categorized under the umbrella term frameshift or truncating variants (FTVs), which includes both PTVs and DNA variants caused by frameshift mutation.

Implication in diseases/disorders

It was believed that protein-truncating variants are not associated with human diseases. Recent studies have implied the involvement of PTVs in autism spectrum disorder.^[6]

Notes and References

1. Rivas. M. A.. Pirinen. M.. Conrad. D. F.. Lek. M.. Tsang. E. K.. Karczewski. K. J.. Maller. J. B.. Kukurba. K. R.. DeLuca. D. S.. 2015-05-08. Effect of predicted protein-truncating genetic variants on the human transcriptome. Science. 348. 6235. 666–669. 10.1126/science.1261877. 0036-8075. 4537935. 25954003. 2015Sci...348..666R.
2. Stenson. Peter D.. Mort. Matthew. Ball. Edward V.. Shaw. Katy. Phillips. Andrew D.. Cooper. David N.. January 2014. The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine. Human Genetics. 133. 1. 1–9. 10.1007/s00439-013-1358-4. 0340-6717. 3898141. 24077912.
3. Easton . Douglas F. . Dunning . Alison M. . 2017-11-01 . Journal of Medical Genetics . 54 . 11 . . 732–741 . en . 10.1136/jmedgenet-2017-104588 . 28779002 . 5740532 . Pharoah . Paul DP . Ostrander . Elaine A. . Luben . Robert . Brown . Judith . Conroy . Don M. . Baynes . Caroline . Ahmed . Shahana.
4. Medical relevance of protein-truncating variants across 337,205 individuals in the UK Biobank study. - PubMed - NCBI . Nature Communications. 9. 1. 1612. pubmeddev . al . DeBoever C., et . en . 29691392. 5915386. 2018. 10.1038/s41467-018-03910-9.
5. Effect of predicted protein-truncating genetic variants on the human transcriptome . MacArthur . Daniel G. . Lappalainen . Tuuli . 2015-05-08 . 348 . 6235 . . 666–669 . en . 10.1126/science.1261877 . 25954003 . 4537935 . Montgomery . Stephen B. . McCarthy . Mark I. . Dermitzakis . Emmanouil T. . Sammeth . Michael . Ardlie . Kristin . Donnelly . Peter . Guigo . Roderic. 2015Sci...348..666R .
6. Book: De Rubeis, S He, X Goldberg, AP Poultney, CS Samocha, K Cicek, AE Kou, Y Liu, L Fromer, M Walker, S Singh, T Klei, L Kosmicki, J Shih-Chen, F Aleksic, B Biscaldi, M Bolton, PF Brownfeld, JM Cai, J Campbell, NG Carracedo, A Chahrour, MH Chiocchetti, AG Coon, H Crawford, EL Curran, SR Dawson, G Duketis, E Fernandez, BA Gallagher, L Geller, E Guter, SJ Hill, RS Ioniță-Laza, J Jimenz Gonzalez, P Kilpinen, H Klauck, SM Kolevzon, A Lee, I Lei, I Lei, J Lehtimäki, T Lin, C-F Ma'ayan, A Marshall, CR McInnes, AL Neale, B Owen, MJ Ozaki, N Parellada, M Parr, JR Purcell, S Puura, K Rajagopalan, D Rehnström, K Reichenberg, A Sabo, A Sachse, M Sanders, SJ Schafer, C Schulte-Rüther, M Skuse, D Stevens, C Szatmari, P Tammimies, K Valladares, O Voran, A Li-San, W Weiss, LA Willsey, AJ Yu, TW Yuen, RKC DDD Study, Homozygosity Mapping Collaborative for Autism, UK10K Consortium, Cook, EH Freitag, CM Gill, M Hultman, CM Lehner, T Palotie, A Schellenberg, GD Sklar, P State, MW Sutcliffe, JS Walsh, CA Scherer, SW Zwick, ME Barett, JC Cutler, DJ Roeder, K Devlin, B Daly, MJ Buxbaum, JD. Synaptic, transcriptional and chromatin genes disrupted in autism.. 2014-11-13. 1031073384.