Pathogenic Variants and Genetic Modifiers
The clinical utility of molecular genetic testing relies on accurate and comprehensive knowledge about the relationships between genes/variants and diseases/symptoms. Correctly interpreting the clinical significance of detected variants continues to be a constant challenge for molecular diagnostic practice. Challenges remain in cases where there is a consensus based on in silico predictors and even validation that the same variants is found in a patient(s) with similar clinical symptoms. One reason for this uncertainty is that single variants do not act alone: interaction among a host of environmental and genetic factors may modify the pathogenic effect of particular variants in different individuals.