The rapid increase in genetic testing in health care has created a large volume of
genetic variants, some of which can pose challenges in classification. As additional
population and disease-specific data become available, computational tools evolve,
and functional data are generated, variant classification can change. For example,
of 100 participants who underwent genomic sequencing in the MedSeq study, 13% received
updated interpretations of originally identified variants after a mean of 13 months
from when the original results were generated.
1
Similarly, in a study of women who had undergone BRCA1/2 testing, 12.4% of variants were reinterpreted over a 5-year period.
2
In another study, reinterpretation of reported variants in 185 pediatric patients
with epilepsy 2 to 5 years after initial testing resulted in reclassification in 36.2%
of cases.
3
In these and similar studies, most reinterpretations involved variants of uncertain
significance (VUS), most of which were reclassified to likely benign/benign. These
examples illustrate the dynamic nature of sequence data interpretation and highlight
the importance of tracking, updating, and reporting these data.- Sorelle J.A.
- Thodeson D.M.
- Arnold S.
- Gotway G.
- Park J.Y.
Clinical utility of reinterpreting previously reported genomic epilepsy test results
for pediatric patients.
JAMA Pediatr. 2019; 173e182302https://doi.org/10.1001/jamapediatrics.2018.2302
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Article info
Publication history
Published online: February 04, 2023
Accepted:
February 1,
2023
Received in revised form:
January 30,
2023
Received:
August 29,
2022
Identification
Copyright
© 2023 American College of Medical Genetics and Genomics. Published by Elsevier Inc. All rights reserved.
