Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000564876 | SCV000667740 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-13 | criteria provided, single submitter | clinical testing | The p.P1666R variant (also known as c.4997C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 4997. The proline at codon 1666 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV002232130 | SCV001557177 | uncertain significance | Familial adenomatous polyposis 1 | 2022-10-08 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1666 of the APC protein (p.Pro1666Arg). 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: 482472). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (rs764731359, gnomAD 0.0009%). |
| Color Diagnostics, |
RCV000564876 | SCV004361478 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-11-02 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with arginine at codon 1666 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with thyroid cancer (PMID: 29684080). This variant has been identified in 1/250338 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. |