Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002358029 | SCV002655119 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-27 | criteria provided, single submitter | clinical testing | The p.P2002R variant (also known as c.6005C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 6005. The proline at codon 2002 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is well 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. |
| Labcorp Genetics |
RCV003776197 | SCV002950602 | uncertain significance | Familial adenomatous polyposis 1 | 2022-12-11 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 1751042). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (rs776504812, gnomAD no frequency). This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 2002 of the APC protein (p.Pro2002Arg). |