Observed frequency and challenges of variant reclassification in a hereditary cancer clinic

Sarah Macklin, Nisha Durand, Paldeep Atwal, Stephanie Hines

Research output: Contribution to journalArticlepeer-review

36 Scopus citations


Purpose: Efforts have been made by the American College of Medical Genetics and Genomics and the Association for Molecular Pathology to make variant classification more uniform, but many limitations remain. Reclassification of a variant of uncertain significance (VUS) is expected, but other more certain calls, like pathogenic or benign, can also be reclassified once additional information is gathered. Variant reclassification can create difficult circumstances for both patients and clinicians. Methods: Retrospective review of all variant reclassifications in genes associated with hereditary cancer syndromes at one clinic between September 2013 and February 2017 was completed. All variant reclassifications were completed and reported by the original testing laboratory. Results: A total of 1,103 hereditary cancer tests were ordered. Fewer than 5% (40/1,103) of the initial reports were updated during that time period. Most reclassifications (29/40) were downgrades of VUS to likely benign. Only three reclassifications could potentially alter medical management. Conclusion: The majority of variant reclassifications do not impact medical management. Upgrading a variant call to pathogenic could be important for a patient's care and shows the importance of open communication between laboratories and clinicians. A variant downgrade from pathogenic can be a significant reclassification as well, especially if prophylactic surgery has been completed.

Original languageEnglish (US)
Pages (from-to)346-350
Number of pages5
JournalGenetics in Medicine
Issue number3
StatePublished - Mar 1 2018


  • hereditary cancer clinic
  • hereditary cancer syndrome
  • variant classification
  • variant of uncertain significance
  • variant reclassification

ASJC Scopus subject areas

  • Genetics(clinical)


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