From the Guidelines
Variants of Unknown Significance (VUS) in the Nebulin (NEB) and Glucosamine (N-Acetyltransferase) (GNE) genes represent genetic changes with insufficient data to determine their pathogenicity, and therefore, should not be used for clinical decision making. The NEB gene provides instructions for making the protein nebulin, which is essential for proper muscle function, and mutations can cause nemaline myopathy, a disorder characterized by muscle weakness 1. The GNE gene encodes an enzyme involved in sialic acid production, and mutations can lead to GNE myopathy (also called hereditary inclusion body myopathy), a progressive muscle disorder. Some key points to consider when dealing with VUS in these genes include:
- The lack of clear evidence linking the variant to disease creates clinical uncertainty 1
- Healthcare providers cannot determine if the variant is causing symptoms or is a benign variation 1
- Patients with a VUS should work with genetic counselors and neuromuscular specialists for appropriate monitoring and follow-up testing
- Family studies may help clarify the significance of the variant, and periodic reassessment is recommended as scientific knowledge advances 1
- The interpretation of these variants may change over time as more research becomes available, and it is essential to resist the temptation to act on uncertain genetic test results 1.
From the Research
Definition of Variants of Unknown Significance (VUS)
- Variants of Unknown Significance (VUS) refer to genetic variants that have been identified through testing, but their significance or impact on an individual's health is not yet fully understood 2, 3, 4, 5, 6.
- VUS are often reported in genetic testing, but they cannot be acted upon clinically, which may delay or prohibit precise diagnosis and genetic counseling 2.
VUS in the Nebulin (NEB) and Glucosamine (N-Acetyltransferase) (GNE) genes
- There is no specific information available in the provided studies regarding the meaning of VUS in the Nebulin (NEB) and Glucosamine (N-Acetyltransferase) (GNE) genes.
- However, the studies suggest that VUS can be found in various genes and that their classification and interpretation can be challenging 2, 3, 4, 5, 6.
Classification and Interpretation of VUS
- The classification and interpretation of VUS can be complex and may require the use of various lines of evidence, including genetic counseling, allele frequency comparison, and functional assays 2, 3.
- The use of VUS subclasses can help prioritize investigation and guide reporting decisions, and may influence medical decision-making despite appreciated uncertainty 3.
- Patients with VUS may experience higher genetic test-specific concerns and may be less likely to have a change in their clinical management compared to patients with positive or negative results 4.