Lab Med Online.  2022 Jul;12(3):145-158. 10.47429/lmo.2022.12.3.145.

Applying Functional Assay Evidence to Interpret Sequence Variants Identified in Hereditary Cancer Genes

• Choi YJ
• Kim B
• Kim Y
• Shin S
• Lee KA

• KMID: 2538599
• DOI: http://doi.org/10.47429/lmo.2022.12.3.145

Abstract

The demand for the interpretation of sequence variants identified by next-generation sequencing is gradually increasing in clinical laboratories. The American College of Medical Genetics and the Association for Molecular Pathology (ACMG/AMP) 2015 guidelines provide a basis for using functional assays as strong evidence for variant classification. However, it is challenging to use the evidence because the protein’s function and the functional assays used to prove it are too diverse. Therefore, this study reviewed various functional assays that can aid in classifying sequence variants in clinical laboratories. This review focuses on the 1) general functional assays associated with basic protein functions and processing and 2) functional assays related to the specific pathogenic mechanisms of four genes (TP53, BRCA1, CDH1, and PTEN) associated with hereditary cancer.

Keyword

Functional assay; Variant interpretation; Hereditary cancer; Variant of uncertain significance

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