Conflicting Interpretations of Genetic Findings on Multiplex Testing in Clinical Practice
In a study reported in the Journal of Clinical Oncology, Balmaña et al found that conflicting interpretations of findings on multiplex testing for cancer genes are fairly common among reporting laboratories and may have implications for medical management decisions.
Study Details
The study assessed genetic variant interpretations from Clinical Laboratory Improvement Amendments–approved commercial clinical laboratories reported to the online genetic registry Prospective Registry of Multiplex Testing (PROMPT). Among 1,191 individuals with clinical data and genetic testing results enrolled in PROMPT between September 2014 and October 2015, 518 participants with 603 genetic variants had a result interpreted by > 1 laboratory, including ≥ 1 submitted to the publicly available ClinVar database.
Interpretation Differences
Among the 603 variants, 221 (37%) were classified as a variant of uncertain significance, 191 (32%) were classified as pathogenic, and 34 (6%) were classified as benign. Differences in interpretation among reporting laboratories were present for 155 variants (26%). Conflicting interpretations were most common for CHEK2 (26%) and ATM (20%), followed by RAD51C (8%), PALB2 (7%), BARD1 (5%), and NBN and APC (4%). Among the 518 participants, 56 (11%) had a variant with conflicting interpretations, ranging from pathogenic/likely pathogenic to variant of uncertain significance.
The investigators concluded: “Conflicting interpretation of genetic findings from multiplex panel testing used in clinical practice is frequent and may have implications for medical management decisions.”
Judith Balmaña, MD, PhD, of Vall d’Hebron Institute of Oncology, Barcelona, Spain, is the corresponding author of the Journal of Clinical Oncology article.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
