Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000470487 | SCV000552757 | uncertain significance | Familial adenomatous polyposis 1 | 2016-11-08 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with alanine at codon 2623 of the APC protein (p.Thr2623Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with an APC-related disease. 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. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Color | RCV000775753 | SCV000910187 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-10-01 | criteria provided, single submitter | clinical testing |