Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000195952 | SCV000254019 | uncertain significance | Familial adenomatous polyposis 1 | 2018-07-03 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with lysine at codon 1663 of the APC protein (p.Glu1663Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs758987855, ExAC 0.009%) but has not been reported in the literature in individuals with a APC-related disease. ClinVar contains an entry for this variant (Variation ID: 216168). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). In summary, this variant is a rare missense change with uncertain impact on 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. |
| Ambry Genetics | RCV000568323 | SCV000667460 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-12-08 | criteria provided, single submitter | clinical testing | Insufficient evidence |