Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001022463 | SCV001184203 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-03-19 | criteria provided, single submitter | clinical testing | The p.V1476L variant (also known as c.4426G>C), located in coding exon 15 of the APC gene, results from a G to C substitution at nucleotide position 4426. The valine at codon 1476 is replaced by leucine, an amino acid with highly similar properties. 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 | RCV003769560 | SCV002134323 | uncertain significance | Familial adenomatous polyposis 1 | 2021-06-21 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with leucine at codon 1476 of the APC protein (p.Val1476Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 824883). This variant is not present in population databases (ExAC no frequency). |