Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002523398 | SCV000552726 | uncertain significance | Familial adenomatous polyposis 1 | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 393 of the APC protein (p.Ser393Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 411526). 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000506739 | SCV000600037 | uncertain significance | not specified | 2017-05-18 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000775759 | SCV000910197 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-31 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000775759 | SCV004001052 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-09 | criteria provided, single submitter | clinical testing | The p.S393P variant (also known as c.1177T>C), located in coding exon 9 of the APC gene, results from a T to C substitution at nucleotide position 1177. The serine at codon 393 is replaced by proline, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |