Appendix: Interpretation of Sequence Analysis Results

Types of sequence variants that may be detected ¹

• Pathogenic sequence variants reported in the literature
• Sequence variants predicted to be pathogenic but not reported in the literature
• Variants of unknown clinical significance ²
• Sequence variants predicted to be likely benign but not reported in the literature
• Benign sequence variants reported in the literature or in population databases

Possibilities when a sequence variant is not detected

• Patient does not have a pathogenic variant in the tested gene (e.g., a sequence variant exists in another gene at another locus).
• Patient has a sequence variant that cannot be detected by sequence analysis (e.g., a large deletion).
• Patient has a sequence variant in a region of the gene (e.g., an intron or regulatory region) not covered by the laboratory's test.

1. Adapted from Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology [2015]

2. Family studies may be used to determine if a sequence variant segregates with the phenotype or occurred de novo.