Interpreting the functional impact of genetic variants: The need for context qualifiers.

American journal of human genetics
Authors
Keywords
Abstract

Genetic alterations influence biological function through a variety of molecular mechanisms. While common functional descriptions (such as loss of function and gain of function) are useful, they may fail to capture mechanistic complexity, particularly in cases of pleiotropy and context-dependent variant effects. To improve variant interpretation and classification, we propose a framework incorporating "context qualifiers" to address mechanistic specificity. This perspective explores the limitations of common functional descriptors and discusses the criteria needed to implement context qualifiers in variant interpretation frameworks to enhance precision medicine applications.

Year of Publication
2025
Journal
American journal of human genetics
Date Published
12/2025
ISSN
1537-6605
DOI
10.1016/j.ajhg.2025.11.007
PubMed ID
41330372
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