Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001025414 | SCV001187597 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-07 | criteria provided, single submitter | clinical testing | The p.K2189R variant (also known as c.6566A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 6566. The lysine at codon 2189 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. 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. |
| Color Diagnostics, |
RCV001025414 | SCV002053626 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-13 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with arginine at codon 2189 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/249068 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Sema4, |
RCV001025414 | SCV002528798 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-02 | criteria provided, single submitter | curation | |
| Labcorp Genetics |
RCV002552396 | SCV003330501 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-25 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 2189 of the APC protein (p.Lys2189Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with APC-related conditions. ClinVar contains an entry for this variant (Variation ID: 826485). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt APC protein function with a negative predictive value of 95%. 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. |
| Baylor Genetics | RCV002552396 | SCV004197597 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-27 | criteria provided, single submitter | clinical testing |