The test will be resulted with the following as appropriate:
Positive for a deleterious mutation: Includes all nonsense and frameshift mutations in APC that occur at or before amino acid 2644 (based on documentation of deleterious mutations in APC).
In addition, specific missense mutations and non-coding intervening sequence (IVS) mutations are recognized as deleterious on the basis of data derived from linkage analysis of high risk families, functional assays, biochemical evidence and/or demonstration of abnormal mRNA transcript processing.
Deletions and duplications of an entire exon(s) identified by Southern blot analysis may also be interpreted to be deleterious. Deleterious large genomic rearrangements include single exon and multi exonic deletions and duplications that are out of frame. In frame deletions/duplications are interpreted on an individual basis and the specific evidence supporting the classification of these mutations is included in the individual patient report.
Genetic variant, suspected deleterious: Includes genetic variants for which the available evidence indicates a likelihood, but not proof, that the mutation is deleterious. The specific evidence supporting such an interpretation will be summarized for individual variants on each such report.
Genetic variant, favor polymorphism: Includes genetic variants for which available evidence indicates that the variant is highly unlikely to contribute substantially to cancer risk. The specific evidence supporting such an interpretation will be summarized for individual variants on each such report.
Genetic variant of uncertain significance: Includes missense mutations and mutations that occur in analyzed intronic regions whose clinical significance has not yet been determined, as well as nonsense and frameshift mutations that occur distal to amino acid position 2644 in APC.
A genetic variant of uncertain significance in APC is considered less likely to be deleterious if it has been observed in one or more individuals with a known deleterious mutation in the same gene.
No deleterious mutation detected: Includes non-truncating genetic variants observed at an allele frequency of approximately 1% of a suitable control population (providing that no data suggest clinical significance), as well as all genetic variants for which published data demonstrate absence of substantial clinical significance. Also includes mutations in the protein-coding region that neither alter the amino acid sequence nor are predicted to significantly affect exon splicing, and base pair alterations in non-coding portions of the gene that have been demonstrated to have no deleterious effect on the length or stability of the mRNA transcript. Data on polymorphic variants are available upon request.
There may be uncommon genetic abnormalities in APC that will not be detected by Colaris AP (see Limitations of Method). This analysis, however, is believed to rule out the majority of abnormalities in this gene, which is believed to be responsible for most Familial Adenomatous Polyposis (FAP) and attenuated FAP (AFAP).
Y165C and G382D in MYH were not detected: There may be other mutations in MYH that were not detected because this test was designed to detect Y165C and G382D.
Specific variant/mutation not identified: Indicates that specific and designated mutations or variants are not present in the individual being tested. If a specific deleterious mutation has been identified in a family member, a negative analysis for the specific mutation indicates that the tested individual is at the general population risk of developing those cancers and benign findings associated with FAP and AFAP.
Positive for two MYH mutations: Includes observations of Y165C and G382D together, or observations of two alleles of Y165C or G382D. The presence of these two MYH mutations has been documented in recent literature to be associated with colorectal polyposis and cancer.
One MYH mutation detected, colorectal polyposis and cancer risk unknown: Includes observations of one allele of Y165C or G382D. It is currently unknown whether individuals who carry a single MYH mutation are at some measure of increased risk for colorectal polyposis and cancer. Patients with one MYH mutation will automatically receive full sequence analysis of the MYH gene (see MYH Technical Specifications).