Non-Public Variant Reporting Hampers Consistency of Sequence Interpretation Between Labs

Discrepancies in the interpretation of variants between laboratories occurs in more than half the samples, according to a study published in the January issue of Genetics in Medicine. Alarmingly, many of these discrepant interpretations could significantly affect diagnosis or recommendations for clinical care. Standardization of variant interpretation could benefit from expansion of publicly available variant catalogs through mandatory reporting, standards for the use of investigative algorithms, and inclusion of predicted protein consequences in variant and clinical databases, the authors suggest. The Collagen Diagnostic Laboratory (CDL; Seattle, Wash.), is a research and clinical laboratory specializing in heritable connective-tissue disorders. It commonly receives requests to provide "second opinion" on variants identified by outside laboratories (OLs). Over a 14-month period, CDL received 38 of these requests for interpretation. Interpretations by the two laboratories were compared and discrepancies were assessed. OL reports were reviewed for sources and tools used in interpretation to understand the reason for discordance between the labs. The researchers found that the original genetic testing was completed in five private commercial laboratories (20 sample inquiries), six academic laboratories (12 sample inquiries), and six unidentified laboratories. Gene interrogation at the OL used exome sequencing (n = 6), next-generation sequencing panel (n = […]