Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001012786 | SCV001173286 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-24 | criteria provided, single submitter | clinical testing | The p.S568N variant (also known as c.1703G>A), located in coding exon 13 of the APC gene, results from a G to A substitution at nucleotide position 1703. The serine at codon 568 is replaced by asparagine, an amino acid with highly similar properties. In one study, this alteration was detected in a patient with colorectal cancer at age 32 (Kayser K et al. Int J Cancer, 2018 12;143:2800-2813). In another study, this alteration was not seen in 732 breast cancer patients or 189 colorectal cancer patients but was detected in 1/490 cancer-free elderly controls in a Turkish population (Akcay IM et al. Int J Cancer, 2021 01;148:285-295). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003649187 | SCV001223058 | uncertain significance | Familial adenomatous polyposis 1 | 2023-11-02 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 568 of the APC protein (p.Ser568Asn). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with colorectal cancer (PMID: 29987844). ClinVar contains an entry for this variant (Variation ID: 819869). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function with a negative predictive value of 95%. 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. |
| Sema4, |
RCV001012786 | SCV002527035 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-09 | criteria provided, single submitter | curation | |
| Center for Genomic Medicine, |
RCV003320781 | SCV004025043 | uncertain significance | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV002550779 | SCV004203969 | uncertain significance | Familial adenomatous polyposis 1 | 2023-07-05 | criteria provided, single submitter | clinical testing |