Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003742598 | SCV000647221 | uncertain significance | Familial adenomatous polyposis 1 | 2017-01-23 | criteria provided, single submitter | clinical testing | In summary, this is a novel intronic change with uncertain impact on splicing. It has been classified as a Variant of Uncertain Significance. This sequence change falls in intron 3 of the APC gene. It does not directly change the encoded amino acid sequence of the APC protein. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a APC-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. |
| Ambry Genetics | RCV002431655 | SCV002729634 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-19 | criteria provided, single submitter | clinical testing | The c.221-5T>G intronic variant results from a T to G substitution 5 nucleotides upstream from coding exon 3 in the APC gene. This alteration has been observed in at least one individual with a personal and/or family history that is consistent with APC-related disease (Ambry internal data). This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site and will result in the creation or strengthening of a novel splice acceptor site; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |