Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000574304 | SCV000667759 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-15 | criteria provided, single submitter | clinical testing | The p.S643P variant (also known as c.1927T>C), located in coding exon 14 of the APC gene, results from a T to C substitution at nucleotide position 1927. The serine at codon 643 is replaced by proline, an amino acid with similar properties. This alteration has been reported in an individual with colorectal adenoma but without a polyposis phenotype (Azzopardi D et al. Cancer Res. 2008 Jan;68:358-63). 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. |
| Invitae | RCV003534324 | SCV000948223 | uncertain significance | Familial adenomatous polyposis 1 | 2023-08-09 | 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 643 of the APC protein (p.Ser643Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with multiple colorectal polyps (PMID: 18199528). ClinVar contains an entry for this variant (Variation ID: 82615). 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. |
| Systems Biology Platform Zhejiang California International Nano |
RCV000073604 | SCV000105195 | cancer | Familial colorectal cancer | no assertion criteria provided | not provided | Converted during submission to other. |