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. 2019 Aug;27(8):1197-1214.
doi: 10.1038/s41431-019-0384-7. Epub 2019 Apr 24.

Secondary actionable findings identified by exome sequencing: expected impact on the organisation of care from the study of 700 consecutive tests

Christel Thauvin-Robinet  1   2   3   4 , Julien Thevenon  5   6   7   8 , Sophie Nambot  6   7 , Julian Delanne  7 , Paul Kuentz  5   6 , Ange-Line Bruel  5   6   8 , Aline Chassagne  5   9 , Elodie Cretin  5   9 , Aurore Pelissier  5   10 , Chritine Peyron  5   10 , Elodie Gautier  5 , Daphné Lehalle  6   7 , Nolwenn Jean-Marçais  7 , Patrick Callier  5   6   8 , Anne-Laure Mosca-Boidron  5   6   8 , Antonio Vitobello  5   6   8 , Arthur Sorlin  5   6   7   8 , Frédéric Tran Mau-Them  5   6   8 , Christophe Philippe  5   6   8 , Pierre Vabres  5   6 , Laurent Demougeot  11 , Charlotte Poé  6 , Thibaud Jouan  6 , Martin Chevarin  6 , Mathilde Lefebvre  6   7 , Marc Bardou  12 , Emilie Tisserant  6 , Maxime Luu  12 , Christine Binquet  12 , Jean-François Deleuze  13 , Céline Verstuyft  14 , Yannis Duffourd  5   6 , Laurence Faivre  15   16   17   18
Affiliations

Secondary actionable findings identified by exome sequencing: expected impact on the organisation of care from the study of 700 consecutive tests

Christel Thauvin-Robinet et al. Eur J Hum Genet. 2019 Aug.

Abstract

With exome/genome sequencing (ES/GS) integrated into the practice of medicine, there is some potential for reporting incidental/secondary findings (IFs/SFs). The issue of IFs/SFs has been studied extensively over the last 4 years. In order to evaluate their implications in care organisation, we retrospectively evaluated, in a cohort of 700 consecutive probands, the frequency and burden of introducing the search for variants in a maximum list of 244 medically actionable genes (genes that predispose carriers to a preventable or treatable disease in childhood/adulthood and genes for genetic counselling issues). We also focused on the 59 PharmGKB class IA/IB pharmacogenetic variants. We also compared the results in different gene lists. We identified variants (likely) affecting protein function in genes for care in 26 cases (3.7%) and heterozygous variants in genes for genetic counselling in 29 cases (3.8%). Mean time for the 700 patients was about 6.3 min/patient for medically actionable genes and 1.3 min/patient for genes for genetic counselling, and a mean time of 37 min/patients for the reinterpreted variants. These results would lead to all 700 pre-test counselling sessions being longer, to 55 post-test genetic consultations and to 27 secondary specialised medical evaluations. ES also detected 42/59 pharmacogenetic variants or combinations of variants in the majority of cases. An extremely low metabolizer status in genes relevant for neurodevelopmental disorders (CYP2C9 and CYP2C19) was found in 57/700 cases. This study provides information regarding the need to anticipate the implementation of genomic medicine, notably the work overload at various steps of the process.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1
Scheme of the “disease” gene list developed to gather actionable genes from the different previously published genes list [, , –20]
Fig. 2
Fig. 2
Scheme of interpretation results of the 73 variants among the 244 genes and variants of interest, from the cohort of 700 cases, and their repercussions on patient care
See this image and copyright information in PMC

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