Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003537458 | SCV001230777 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-11 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 121 of the APC protein (p.Arg121Lys). This variant is present in population databases (rs193049694, gnomAD 0.003%). 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: 859634). 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. 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. |
| Color Diagnostics, |
RCV001186320 | SCV001352704 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-19 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001186320 | SCV002614165 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-01-17 | criteria provided, single submitter | clinical testing | The p.R121K variant (also known as c.362G>A), located in coding exon 3 of the APC gene, results from a G to A substitution at nucleotide position 362. The arginine at codon 121 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV002479387 | SCV002774411 | uncertain significance | not provided | 2021-07-21 | criteria provided, single submitter | clinical testing |