Likely Pathogenic, Possibly Pathogenic, or VUS: What’s the Difference?An Experimental Approach to Assess Whether Individuals Discern Differences Between Uncertain Genetic Variant Classifications

uncertain genetic variants;classification;genetic counseling;Genetic Counseling

Hellwig, Lydia DeanneKlein, William M. P. ;

Johns Hopkins University

关键词: uncertain genetic variants;    classification;    genetic counseling;    Genetic Counseling;   

Others  :  https://jscholarship.library.jhu.edu/bitstream/handle/1774.2/40728/HELLWIG-THESIS-2017.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: JOHNS HOPKINS DSpace Repository

【 摘 要 】

Background: ACMG guidelines suggest that clinical laboratories use a variant classification system that includes five categories. Some laboratories use their own classification systems that divide variants of uncertain significance (VUS) into subcategories. There is little literature regarding patient perceived differences among the five ACMG categories of variants, and no literature on their perceptions of the subcategories of uncertain genetic test results.Objective: To determine whether patients perceive differences in different classifications of genetic variants, by measuring risk comprehension, risk perception, worry, perceived uncertainty, and behavioral intentions.Methods: Randomized hypothetical genetic test results were given to each participant enrolled in a genome sequencing study. Three categories of variants were presented to participants: Variant of Uncertain Significance (VUS), Variant- Possibly Pathogenic (VPP), and Variant- Likely Pathogenic (VLP). Results: A total of 291 participants completed the survey. Participants perceived risk to be higher if they received a VPP or VLP than a VUS, but did not perceive uncertainty differently for the variant categories. Behavioral intentions, including screening, sharing with family, seeking genetic counseling, and seeking specialty care were found to be higher for those who received a VPP as compared to those who received a VUS, but were not different between those who received a VPP and a VLP. Participants reported greater worry when they received a VPP than when they received a VUS. In addition, worry and risk perception were found to partially mediate the relationship between the variant classification received and behavioral intentions.Discussion: Our results suggest that sub-classification of uncertain genetic test results affects patient perception of risk, worry, and behavioral intentions, but not uncertainty. In addition, worry and risk perception partially mediate the relationship between genetic variant classification received and behavioral intentions. These findings are important in considering guidelines regarding classification systems and can help inform approaches to risk communication, which is an important component of genetic counseling.