Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000572447 | SCV000672536 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-12-20 | criteria provided, single submitter | clinical testing | The p.P1514S variant (also known as c.4540C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 4540. The proline at codon 1514 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Missense alterations in APC are not a common cause of disease (Spier I et al. Genet Med. 2024 Feb;26(2):100992). Based on the available evidence, the clinical significance of this variant remains unclear. |
| Laboratory for Molecular Medicine, |
RCV000608323 | SCV000712649 | uncertain significance | not specified | 2016-11-25 | criteria provided, single submitter | clinical testing | The p.Pro1514Ser variant in APC has not been previously reported in individuals with hereditary cancer or in large population studies. Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Pro1514Ser variant is uncertain. |
| Color Diagnostics, |
RCV000572447 | SCV000913110 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-09 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV004562461 | SCV000958865 | uncertain significance | Familial adenomatous polyposis 1 | 2024-09-23 | 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 1514 of the APC protein (p.Pro1514Ser). 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: 485110). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |