{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:49:28Z","timestamp":1791492568323,"version":"4.3.4"},"reference-count":3,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T00:00:00Z","timestamp":1791417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Genom. Inform."],"published-print":{"date-parts":[[2026,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Roy et al. reported an extensive computational analysis of nonsynonymous single-nucleotide variants (nsSNPs) in the human\n                    <jats:italic>CYLD<\/jats:italic>\n                    gene and characterized several variants as potentially disease- or cancer-associated. Although such analyses can be valuable for generating hypotheses, computational predictions should be clearly distinguished from clinical or functional evidence. Among the 18 \u201chigh-risk nsSNPs\u201d prioritized by the authors, only p.Glu747Gly (E747G) has established clinical evidence supporting pathogenicity, whereas the remaining variants lack sufficient evidence for pathogenic classification and should be considered variants of uncertain significance pending further evidence. We highlight three major concerns: the lack of independence among some prediction tools used for variant prioritization; the interpretation of somatic mutation clustering as evidence for germline disease association; and the presentation of variants with no established clinical or experimental evidence as disease-associated. Under the ACMG\/AMP framework, computational evidence can provide supporting evidence but cannot substitute for clinical, population, segregation, or functional evidence. We suggest that the terminology and conclusions of the original article be revised to distinguish computationally predicted effects from demonstrated disease associations.\n                  <\/jats:p>","DOI":"10.1186\/s44342-026-00082-7","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T07:16:18Z","timestamp":1791443778000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The risk of over-interpreting in silico predictions as clinical evidence: a comment on Roy et al. (2024)"],"prefix":"10.1186","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9820-0374","authenticated-orcid":false,"given":"Dimitri","family":"Tchernitchko","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"82_CR1","doi-asserted-by":"publisher","DOI":"10.1186\/s44342-024-00007-2","volume":"22","author":"AS Roy","year":"2024","unstructured":"Roy AS, Feroz T, Islam MK, Hasan MA, Islam MA, Alam MS, et al. A computational approach for structural and functional analyses of disease-associated mutations in the human CYLD gene. Genomics Inform. 2024;22:e4.","journal-title":"Genomics Inform"},{"key":"82_CR2","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1046\/j.1523-1747.2003.12514.x","volume":"121","author":"G Hu","year":"2003","unstructured":"Hu G, Onder M, Gill M, Gubanich G, Bickers DR, Karaduman A, et al. A novel missense mutation in CYLD in a family with Brooke-Spiegler syndrome. J Invest Dermatol. 2003;121:732\u20134.","journal-title":"J Invest Dermatol"},{"key":"82_CR3","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1038\/gim.2015.30","volume":"17","author":"S Richards","year":"2015","unstructured":"Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405\u201324.","journal-title":"Genet Med"}],"container-title":["Genomics &amp; Informatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s44342-026-00082-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s44342-026-00082-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s44342-026-00082-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:02:51Z","timestamp":1791489771000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s44342-026-00082-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,8]]},"references-count":3,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,12]]}},"alternative-id":["82"],"URL":"https:\/\/doi.org\/10.1186\/s44342-026-00082-7","relation":{},"ISSN":["1598-866X","2234-0742"],"issn-type":[{"value":"1598-866X","type":"print"},{"value":"2234-0742","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,8]]},"assertion":[{"value":"18 August 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 September 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 October 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The author declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"18"}}