Clinical Correlations:
A small percentage of individuals who are carriers or have a diagnosis of Wilson disease (WD) may have a mutation that is not identified by this method (eg, large genomic deletions, promoter mutations, deep intronic mutations). The absence of a mutation, therefore, does not eliminate the possibility of positive carrier status or the diagnosis of WD. For carrier testing, it is important to first document the presence of an ATP7B gene mutation in an affected family member.
Test results should be interpreted in context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.
Technical Limitations:
In some cases, DNA variants of undetermined significance may be identified.
Due to the limitations of next-generation sequencing, small deletions and insertions may not be detected by this test. If a diagnosis is still suspected, contact a molecular genetic counselor in the Genomics Laboratory at 800-533-1710 for more information regarding follow-up testing options.
Rare polymorphisms exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
Evaluation Tools:
Multiple in-silico evaluation tools were used to assist in the interpretation of these results. These tools are updated regularly; therefore changes to these algorithms may result in different predictions for a given alteration. Additionally, the predictability of these tools for the determination of pathogenicity is currently unvalidated.
Unless reported or predicted to cause disease, alterations that do not result in an amino acid substitution are not reported.
Reclassification of Variants-Policy:
All detected alterations are evaluated according to American College of Medical Genetics and Genomics (ACMG) recommendations. Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. At this time, it is not standard practice for the laboratory to systematically review likely pathogenic alterations or variants of uncertain significance that are detected and reported. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.