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Reinterpretation, reclassification, and its downstream effects: challenges for clinical laboratory geneticists

Reinterpretation, reclassification, and its downstream effects: challenges for clinical laboratory geneticists
Reinterpretation, reclassification, and its downstream effects: challenges for clinical laboratory geneticists
Background: In recent years, the amount of genomic data produced in clinical genetics services has increased significantly due to the advent of next-generation sequencing. This influx of genomic information leads to continuous changes in knowledge on how genetic variants relate to hereditary disease. These changes can have important consequences for patients who have had genetic testing in the past, as new information may affect their clinical management. When and how patients should be recontacted after new genetic information becomes available has been investigated extensively. However, the issue of how to handle the changing nature of genetic information remains underexplored in a laboratory setting, despite it being the first stage at which changes in genetic data are identified and managed. Methods: The authors organized a 7-day online focus group discussion. Fifteen clinical laboratory geneticists took part. All (nine) Dutch clinical molecular genetics diagnostic laboratories were represented. Results: Laboratories in our study reinterpret genetic variants reactively, e.g. at the request of a clinician or following identification of a previously classified variant in a new patient. Participants currently deemed active, periodic reinterpretation to be unfeasible and opinions differed on whether it is desirable, particularly regarding patient autonomy and the main responsibilities of the laboratory. The efficacy of reinterpretation was questioned in the presence of other strategies, such as reanalysis and resequencing of DNA. Despite absence of formal policy regarding when to issue a new report for clinicians due to reclassified genetic data, participants indicated similar practice across all laboratories. However, practice differed significantly between laboratory geneticists regarding the reporting of VUS reclassifications. Conclusion: Based on the results, the authors formulated five challenges needing to be addressed in future laboratory guidelines: 1. Should active reinterpretation of variants be conducted by the laboratory as a routine practice? 2. How does reinterpretation initiated by the laboratory relate to patient expectations and consent? 3. When should reinterpreted data be considered clinically significant and communicated from laboratory to clinician? 4. Should reinterpretation, reanalysis or a new
1755-8794
El Mecky, Julia
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Johansson, Lennart
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Plantinga, Mirjam
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Fenwick, Angela
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Lucassen, Anneke
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Dijkhuizen, Trijnie
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van der Hout, annemieke
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Lyle, Kate
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Van Langen, Irene M.
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El Mecky, Julia
c3ccb80a-1712-4811-8a5a-4dd3d27a564d
Johansson, Lennart
b76e841c-a553-4c5d-8dd5-6264c3d96a12
Plantinga, Mirjam
80329f67-dce0-4e72-ad91-8aff2212dde6
Fenwick, Angela
95a1f4fa-7f6f-4c07-a93b-9ea39c231c31
Lucassen, Anneke
2eb85efc-c6e8-4c3f-b963-0290f6c038a5
Dijkhuizen, Trijnie
fde19741-c18b-487f-be9e-e9fb36d8a160
van der Hout, annemieke
9516dbba-900f-4b06-9d53-a730fd737235
Lyle, Kate
ff88e501-884c-423a-8050-f915fc19f0a8
Van Langen, Irene M.
bcc17f78-800f-4deb-ac58-7c7e2f408bc7

El Mecky, Julia, Johansson, Lennart, Plantinga, Mirjam, Fenwick, Angela, Lucassen, Anneke, Dijkhuizen, Trijnie, van der Hout, annemieke, Lyle, Kate and Van Langen, Irene M. (2019) Reinterpretation, reclassification, and its downstream effects: challenges for clinical laboratory geneticists. BMC Medical Genomics, [170]. (doi:10.1186/s12920-019-0612-6).

Record type: Article

Abstract

Background: In recent years, the amount of genomic data produced in clinical genetics services has increased significantly due to the advent of next-generation sequencing. This influx of genomic information leads to continuous changes in knowledge on how genetic variants relate to hereditary disease. These changes can have important consequences for patients who have had genetic testing in the past, as new information may affect their clinical management. When and how patients should be recontacted after new genetic information becomes available has been investigated extensively. However, the issue of how to handle the changing nature of genetic information remains underexplored in a laboratory setting, despite it being the first stage at which changes in genetic data are identified and managed. Methods: The authors organized a 7-day online focus group discussion. Fifteen clinical laboratory geneticists took part. All (nine) Dutch clinical molecular genetics diagnostic laboratories were represented. Results: Laboratories in our study reinterpret genetic variants reactively, e.g. at the request of a clinician or following identification of a previously classified variant in a new patient. Participants currently deemed active, periodic reinterpretation to be unfeasible and opinions differed on whether it is desirable, particularly regarding patient autonomy and the main responsibilities of the laboratory. The efficacy of reinterpretation was questioned in the presence of other strategies, such as reanalysis and resequencing of DNA. Despite absence of formal policy regarding when to issue a new report for clinicians due to reclassified genetic data, participants indicated similar practice across all laboratories. However, practice differed significantly between laboratory geneticists regarding the reporting of VUS reclassifications. Conclusion: Based on the results, the authors formulated five challenges needing to be addressed in future laboratory guidelines: 1. Should active reinterpretation of variants be conducted by the laboratory as a routine practice? 2. How does reinterpretation initiated by the laboratory relate to patient expectations and consent? 3. When should reinterpreted data be considered clinically significant and communicated from laboratory to clinician? 4. Should reinterpretation, reanalysis or a new

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Accepted/In Press date: 31 October 2019
Published date: 29 November 2019

Identifiers

Local EPrints ID: 436370
URI: http://eprints.soton.ac.uk/id/eprint/436370
ISSN: 1755-8794
PURE UUID: bf1e37d0-5cf6-46b7-a662-d33c653df519
ORCID for Anneke Lucassen: ORCID iD orcid.org/0000-0003-3324-4338

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Date deposited: 09 Dec 2019 17:30
Last modified: 26 Nov 2021 02:45

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Contributors

Author: Julia El Mecky
Author: Lennart Johansson
Author: Mirjam Plantinga
Author: Angela Fenwick
Author: Anneke Lucassen ORCID iD
Author: Trijnie Dijkhuizen
Author: annemieke van der Hout
Author: Kate Lyle
Author: Irene M. Van Langen

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