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Abstract: 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.
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