Protein-truncating variants
Protein-truncating variants (PTVs) are genetic variants predicted to shorten the coding sequence of genes,{{Cite journal|last1=Rivas|first1=M. A.|last2=Pirinen|first2=M.|last3=Conrad|first3=D. F.|last4=Lek|first4=M.|last5=Tsang|first5=E. K.|last6=Karczewski|first6=K. J.|last7=Maller|first7=J. B.|last8=Kukurba|first8=K. R.|last9=DeLuca|first9=D. S.|date=2015-05-08|title=Effect of predicted protein-truncating genetic variants on the human transcriptome|journal=Science|volume=348|issue=6235|pages=666–669|doi=10.1126/science.1261877|issn=0036-8075|pmc=4537935|pmid=25954003|bibcode=2015Sci...348..666R}} through ways like a stop-gain mutation.{{Cite journal|last1=Stenson|first1=Peter D.|last2=Mort|first2=Matthew|last3=Ball|first3=Edward V.|last4=Shaw|first4=Katy|last5=Phillips|first5=Andrew D.|last6=Cooper|first6=David N.|date=January 2014|title=The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine|journal=Human Genetics|volume=133|issue=1|pages=1–9|doi=10.1007/s00439-013-1358-4|issn=0340-6717|pmc=3898141|pmid=24077912}}{{Cite journal |url= |title=Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks |last1=Easton |first1=Douglas F. |last2=Dunning |first2=Alison M. |date=2017-11-01 |journal=Journal of Medical Genetics |volume=54 |issue=11 |publisher=Journal of Medical Genetics, The BMJ |pages=732–741 |language=en |doi=10.1136/jmedgenet-2017-104588 |pmid=28779002 |pmc=5740532 |last3=Pharoah |first3=Paul DP |last4=Ostrander |first4=Elaine A. |last5=Luben |first5=Robert |last6=Brown |first6=Judith |last7=Conroy |first7=Don M. |last8=Baynes |first8=Caroline |last9=Ahmed |first9=Shahana}}{{Cite journal |title=Medical relevance of protein-truncating variants across 337,205 individuals in the UK Biobank study. - PubMed - NCBI |journal = Nature Communications|volume = 9|issue = 1|pages = 1612|last1=pubmeddev |last2=al |first2=DeBoever C., et |language=en |pmid = 29691392|pmc = 5915386|year = 2018|doi = 10.1038/s41467-018-03910-9}}{{Cite journal |title=Effect of predicted protein-truncating genetic variants on the human transcriptome |last1=MacArthur |first1=Daniel G. |last2=Lappalainen |first2=Tuuli |date=2015-05-08 |volume=348 |issue=6235 |journal=Science |pages=666–669 |language=en |doi=10.1126/science.1261877 |pmid=25954003 |pmc=4537935 |last3=Montgomery |first3=Stephen B. |last4=McCarthy |first4=Mark I. |last5=Dermitzakis |first5=Emmanouil T. |last6=Sammeth |first6=Michael |last7=Ardlie |first7=Kristin |last8=Donnelly |first8=Peter |last9=Guigo |first9=Roderic|bibcode=2015Sci...348..666R }} 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.{{Cite book|title=Synaptic, transcriptional and chromatin genes disrupted in autism.|last=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|date=2014-11-13|oclc=1031073384}}