Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003534623 | SCV000822597 | uncertain significance | Familial adenomatous polyposis 1 | 2023-02-24 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2392 of the APC protein (p.Pro2392Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with rectum cancer (PMID: 27978560). ClinVar contains an entry for this variant (Variation ID: 572715). 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. 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. |
| Color Diagnostics, |
RCV001191948 | SCV001359890 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-07-03 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with serine at codon 2392 of the APC protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in an individual affected with cancer of the rectum (PMID: 27978560). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV001191948 | SCV002662800 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-03-23 | criteria provided, single submitter | clinical testing | The p.P2392S variant (also known as c.7174C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 7174. The proline at codon 2392 is replaced by serine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. This alteration was identified in a patient diagnosed with MMR proficient rectal cancer at age 47 (Pearlman R et al. JAMA Oncol 2017 Apr;3:464-471). 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. |