Estimated Filtration: The Continued Need for Expert Classification of Genetic Variants
Authors: Jason L. Vassy
Journal: Annals of Internal Medicine (2018)

Editorials1 January 2019Estimated Filtration: The Continued Need for Expert Classification of Genetic VariantsJason L. Vassy, MD, MPHJason L. Vassy, MD, MPHVA Boston Healthcare System, Harvard Medical School, and Brigham and Women's Hospital, Boston, Massachusetts (J.L.V.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M18-3090 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail The typical Google or Amazon search yields an impossibly large number of results: A recent Google search for “kidney disease” returned 131 000 000. Human readers clearly need to apply a filtering system to find the information or products they seek, using such criteria as source reputation and customer reviews. Even so, some degree of manual inspection is required.The same is true of finding genetic variants that might cause disease, and it is fitting that Rasouly and colleagues (1) illustrate this concept with the human body's own filter: the genitourinary system. The human genome consists of approximately 3 billion base pairs ...References1. Rasouly HM, Groopman EE, Heyman-Kantor R, Fasel DA, Mitrotti A, Westland R, et al. The burden of candidate pathogenic variants for kidney and genitourinary disorders emerging from exome sequencing. Ann Intern Med. 2019;170:11-21. doi:10.7326/M18-1241 LinkGoogle Scholar2. Biesecker LG, Green RC. Diagnostic clinical genome and exome sequencing. N Engl J Med. 2014;370:2418-25. [PMID: 24941179] doi:10.1056/NEJMra1312543 CrossrefMedlineGoogle Scholar3. Kalia SS, Adelman K, Bale SJ, Chung WK, Eng C, Evans JP, et al. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet Med. 2017;19:249-55. [PMID: 27854360] doi:10.1038/gim.2016.190 CrossrefMedlineGoogle Scholar4. Biesecker LG, Nussbaum RL, Rehm HL. Distinguishing variant pathogenicity from genetic diagnosis: how to know whether a variant causes a condition. JAMA. 2018. [PMID: 30326012] doi:10.1001/jama.2018.14900 CrossrefMedlineGoogle Scholar5. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al; ACMG Laboratory Quality Assurance Committee. 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;17:405-24. [PMID: 25741868] doi:10.1038/gim.2015.30 CrossrefMedlineGoogle Scholar6. Christensen KD, Vassy JL, Phillips KA, Blout CL, Azzariti DR, Lu CY, et al. Short-term costs of integrating whole-genome sequencing into primary care and cardiology settings: a pilot randomized trial. Genet Med. 2018. [PMID: 29565423] doi:10.1038/gim.2018.35 CrossrefMedlineGoogle Scholar7. Wainberg M, Merico D, Delong A, Frey BJ. Deep learning in biomedicine. Nat Biotechnol. 2018;36:829-38. [PMID: 30188539] doi:10.1038/nbt.4233 CrossrefMedlineGoogle Scholar8. ClinGen. 2018. Accessed at www.clinicalgenome.org on 4 November 2018. Google Scholar Author, Article, and Disclosure InformationAffiliations: VA Boston Healthcare System, Harvard Medical School, and Brigham and Women's Hospital, Boston, Massachusetts (J.L.V.)Grant Support: By research grant IK2-CX001262 from the VA Office of Research & Development.Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-3090.Corresponding Author: Jason L. Vassy, MD, MPH, 150 South Huntington Avenue, 152-G, Boston, MA 02130; e-mail, [email protected]org.This article was published at Annals.org on 27 November 2018. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Burden of Candidate Pathogenic Variants for Kidney and Genitourinary Disorders Emerging From Exome Sequencing Hila Milo Rasouly , Emily E. Groopman , Reuben Heyman-Kantor , David A. Fasel , Adele Mitrotti , Rik Westland , Louise Bier , Chunhua Weng , Zhong Ren , Brett Copeland , Priya Krithivasan , Wendy K. Chung , Simone Sanna-Cherchi , David B. Goldstein , and Ali G. Gharavi Metrics 1 January 2019Volume 170, Issue 1Page: 64-65KeywordsClinical geneticsDatabasesGenetic determinismGenetic diseasesGenome sequencingGenomicsMedical geneticsPathogensPilot studiesPolycystic kidney disease ePublished: 27 November 2018 Issue Published: 1 January 2019 PDF downloadLoading ...