Different Interpretations of the Same Genetic Data
Authors: Jeffrey A. SoRelle, Amber P. Gemmell, Theodora S. Ross
Journal: Annals of Internal Medicine (2020)

Letters4 August 2020Different Interpretations of the Same Genetic DataJeffrey A. SoRelle, MD, Amber P. Gemmell, MS, CGC, and Theodora S. Ross, MD, PhDJeffrey A. SoRelle, MDUniversity of Texas Southwestern Medical Center, Dallas, Texas (J.A.S.), Amber P. Gemmell, MS, CGCHarold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas (A.P.G., T.S.R.), and Theodora S. Ross, MD, PhDHarold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas (A.P.G., T.S.R.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/L20-0192 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Background: In 2018, we ordered gene testing for 2 Hispanic women in their early 30s who had a family history of cancer. We used a different testing laboratory for each patient. Both laboratories reported the same variant in the CHEK2 gene (c.707T>C). However, one laboratory classified the variant as a likely pathogenic variant, whereas the other laboratory classified it as a variant of uncertain significance. Similar differences have affected an additional 25 patients in our clinic. To the best of our knowledge, the prevalence of this problem is unknown.Objective: To measure the prevalence of different interpretations for the same ...References1. Henrie A, Hemphill SE, Ruiz-Schultz N, et al. ClinVar Miner: Demonstrating utility of a Web-based tool for viewing and filtering ClinVar data. Hum Mutat. 2018;39:1051-1060. [PMID: 29790234] doi:10.1002/humu.23555 CrossrefMedlineGoogle Scholar2. SoRelle JA, Thodeson DM, Arnold S, et al. Clinical utility of reinterpreting previously reported genomic epilepsy test results for pediatric patients. JAMA Pediatr. 2019;173:e182302. [PMID: 30398534] doi:10.1001/jamapediatrics.2018.2302 CrossrefMedlineGoogle Scholar3. Mersch J, Brown N, Pirzadeh-Miller S, et al. Prevalence of variant reclassification following hereditary cancer genetic testing. JAMA. 2018;320:1266-1274. [PMID: 30264118] doi:10.1001/jama.2018.13152 CrossrefMedlineGoogle Scholar4. Delimitsou A, Fostira F, Kalfakakou D, et al. Functional characterization of CHEK2 variants in a Saccharomyces cerevisiae system. Hum Mutat. 2019;40:631-648. [PMID: 30851065] doi:10.1002/humu.23728 CrossrefMedlineGoogle Scholar5. Weitzel JN, Neuhausen SL, Adamson A, et al. Pathogenic and likely pathogenic variants in PALB2, CHEK2, and other known breast cancer susceptibility genes among 1054 BRCA-negative Hispanics with breast cancer. Cancer. 2019;125:2829-2836. [PMID: 31206626] doi:10.1002/cncr.32083 CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: University of Texas Southwestern Medical Center, Dallas, Texas (J.A.S.)Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas (A.P.G., T.S.R.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L20-0192.Corresponding Author: Theodora S. Ross, MD, PhD, Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390; e-mail, theo.[email protected]edu.This article was published at Annals.org on 30 June 2020. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCOL4A4 variant recently identified: lessons learned in variant interpretation—a case reportChallenges in breast cancer genetic testing. A call for novel forms of multidisciplinary care and long-term evaluationThe Challenge of Genetic Variants of Uncertain Clinical Significance A Narrative ReviewWylie Burke, MD, PhD, Erik Parens, PhD, Wendy K. Chung, MD, PhD, Sara M. Berger, MS, CGC, and Paul S. Appelbaum, MD 4 August 2020Volume 173, Issue 3Page: 239-240KeywordsCancer geneticsClinical geneticsClinical laboratoriesDatabasesDisclosureGenetic diseasesGenetic testingGeneticsPathogensResearch laboratories ePublished: 30 June 2020 Issue Published: 4 August 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...