Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002531437 | SCV000812810 | uncertain significance | Familial adenomatous polyposis 1 | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with methionine at codon 1987 of the APC protein (p.Ile1987Met). The isoleucine residue is weakly conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Ambry Genetics | RCV003343987 | SCV004059056 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-24 | criteria provided, single submitter | clinical testing | The p.I1987M variant (also known as c.5961C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 5961. The isoleucine at codon 1987 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV002531437 | SCV004195550 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-23 | criteria provided, single submitter | clinical testing |