Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001023354 | SCV001185218 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-10-01 | criteria provided, single submitter | clinical testing | The p.L1660P variant (also known as c.4979T>C), located in coding exon 15 of the APC gene, results from a T to C substitution at nucleotide position 4979. The leucine at codon 1660 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. |
| Invitae | RCV003649219 | SCV001230201 | uncertain significance | Familial adenomatous polyposis 1 | 2019-04-10 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with proline at codon 1660 of the APC protein (p.Leu1660Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with APC-related conditions. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |