Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003773091 | SCV002266312 | uncertain significance | Familial adenomatous polyposis 1 | 2021-01-07 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine with isoleucine at codon 2010 of the APC protein (p.Lys2010Ile). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and isoleucine. 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 | RCV004656799 | SCV005149387 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-27 | criteria provided, single submitter | clinical testing | The p.K2010I variant (also known as c.6029A>T), located in coding exon 15 of the APC gene, results from an A to T substitution at nucleotide position 6029. The lysine at codon 2010 is replaced by isoleucine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Based on the available evidence, the clinical significance of this alteration remains unclear. |