Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003534698 | SCV000830853 | uncertain significance | Familial adenomatous polyposis 1 | 2019-01-18 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with APC-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 4 of the APC gene. It does not directly change the encoded amino acid sequence of the APC protein. |
| Ambry Genetics | RCV001022105 | SCV001183802 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-02 | criteria provided, single submitter | clinical testing | The c.423-4A>G intronic variant results from an A to G substitution 4 nucleotides upstream from coding exon 4 in the APC gene. This nucleotide position is well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to create a new alternate splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of c.423-4A>G remains unclear. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478436 | SCV004219375 | uncertain significance | not provided | 2023-04-04 | criteria provided, single submitter | clinical testing | To the best of our knowledge, the variant has not been reported in the published literature. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Analysis of this variant using software algorithms for the prediction of the effect of nucleotide changes on APC mRNA splicing yielded inconclusive findings . Based on the available information, we are unable to determine the clinical significance of this variant. |