{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,3,5]],"date-time":"2024-03-05T10:44:15Z","timestamp":1709635455172},"reference-count":16,"publisher":"Cold Spring Harbor Laboratory","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"published-print":{"date-parts":[[2018,10]]},"abstract":"<jats:p>The ClinVar database is a useful tool for patients and physicians to view variant interpretations submitted by clinical and nonclinical labs. However, variants of uncertain significance (VUS) in ClinVar can pose a significant burden on patients. If possible, it is important to resolve discrepancies and uncertainties surrounding interpreted variants. Here we highlight a case of a family who received a report of a variant (c.622A&gt;G, p.Ile208Val) in <jats:italic>BRAF<\/jats:italic> following prenatal RASopathy testing. The variant had been previously classified by our laboratory as a VUS, so the mother contacted our laboratory via ClinVar for further information, which prompted reevaluation of the variant. Multiple sources of case-level data as well as the presence of the variant in the general population yielded sufficient evidence to reclassify the variant as likely benign. This reclassification alleviated significant concern for the family, and the child was born healthy with no clinical manifestations of Noonan syndrome or a RASopathy.<\/jats:p>","DOI":"10.1101\/mcs.a002675","type":"journal-article","created":{"date-parts":[[2018,6,26]],"date-time":"2018-06-26T20:25:20Z","timestamp":1530044720000},"page":"a002675","source":"Crossref","is-referenced-by-count":4,"title":["Reclassification of the <i>BRAF<\/i> p.Ile208Val variant by case-level data sharing"],"prefix":"10.1101","volume":"4","author":[{"given":"Andrew R.","family":"Grant","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah E.","family":"Hemphill","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa M.","family":"Vincent","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heidi L.","family":"Rehm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"246","published-online":{"date-parts":[[2018,6,26]]},"reference":[{"key":"2021112506161129000_4.5.a002675.1","first-page":"a002345","article-title":"Points to consider for sharing variant-level information from clinical genetic testing to ClinVar","volume":"4","year":"2017","journal-title":"Cold Spring Harb Mol Case Stud"},{"key":"2021112506161129000_4.5.a002675.2","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12257"},{"key":"2021112506161129000_4.5.a002675.3","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1016\/j.ajhg.2016.09.015","article-title":"Reassessment of genomic sequence variation to harmonize interpretation for personalized medicine","volume":"99","year":"2016","journal-title":"Am J Hum Genet"},{"key":"2021112506161129000_4.5.a002675.4","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2018.3"},{"key":"2021112506161129000_4.5.a002675.5","doi-asserted-by":"crossref","first-page":"1755","DOI":"10.1016\/j.jid.2016.05.095","article-title":"RASopathy gene mutations in melanoma","volume":"136","year":"2016","journal-title":"J Invest Dermatol"},{"key":"2021112506161129000_4.5.a002675.6","doi-asserted-by":"crossref","first-page":"1096","DOI":"10.1038\/gim.2017.14","article-title":"Clinical laboratories collaborate to resolve differences in variant interpretations submitted to ClinVar","volume":"19","year":"2017","journal-title":"Genet Med"},{"key":"2021112506161129000_4.5.a002675.7","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3760"},{"key":"2021112506161129000_4.5.a002675.8","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-06-0433"},{"key":"2021112506161129000_4.5.a002675.9","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2011.05.024"},{"key":"2021112506161129000_4.5.a002675.10","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0223(199907)19:7<642::AID-PD610>3.0.CO;2-1"},{"key":"2021112506161129000_4.5.a002675.11","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2008.057653"},{"key":"2021112506161129000_4.5.a002675.12","doi-asserted-by":"publisher","DOI":"10.1038\/ng2078"},{"key":"2021112506161129000_4.5.a002675.13","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"2021112506161129000_4.5.a002675.14","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20955"},{"key":"2021112506161129000_4.5.a002675.15","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.1016\/j.ophtha.2016.06.061","article-title":"Ocular manifestations of Noonan syndrome: a prospective clinical and genetic study of 25 patients","volume":"123","year":"2016","journal-title":"Ophthalmology"},{"key":"2021112506161129000_4.5.a002675.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2003.11.032"}],"container-title":["Molecular Case Studies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/mcs.a002675","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T14:16:33Z","timestamp":1637849793000},"score":1,"resource":{"primary":{"URL":"http:\/\/molecularcasestudies.cshlp.org\/lookup\/doi\/10.1101\/mcs.a002675"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,26]]},"references-count":16,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2018,10,1]]},"published-print":{"date-parts":[[2018,10]]}},"alternative-id":["10.1101\/mcs.a002675"],"URL":"https:\/\/doi.org\/10.1101\/mcs.a002675","relation":{},"ISSN":["2373-2865","2373-2873"],"issn-type":[{"value":"2373-2865","type":"print"},{"value":"2373-2873","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,26]]}}}