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We found that 43.26% (77 out of 178 in HGMD) and 41.9% (221 out of 528 in ClinVar) of the disease-related missense mutations were associated with higher protein structure destabilizing effects. Overall, most mutations destabilizing the MYO7A protein were found to associate with USH1 and USH1B. Particularly, motor domain and MyTH4 domains were found to be most susceptible to mutations causing the USH1B phenotype. Our work contributes to the understanding of inherited disease from the atomic level of protein structure and analysis of the impact of genetic mutations on protein stability and genotype-to-phenotype relationships in human disease.<\/jats:p>","DOI":"10.15406\/japlr.2021.10.00364","type":"journal-article","created":{"date-parts":[[2021,3,17]],"date-time":"2021-03-17T12:49:06Z","timestamp":1615985346000},"page":"41-48","update-policy":"http:\/\/dx.doi.org\/10.15406\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Homology modeling and global computational mutagenesis of human myosin VIIa"],"prefix":"10.15406","volume":"10","author":[{"given":"Yuri V","family":"Sergeev","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annapurna","family":"Kuppa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"6139","published-online":{"date-parts":[[2021,3,4]]},"reference":[{"issue":"1","key":"ref0","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1097\/WCO.0b013e3283218807","article-title":"Update on Usher syndrome","volume":"22","author":"Saihan","year":"2009","unstructured":"Z Saihan, AR Webster, L Luxon, et al. 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