Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000571793 | SCV000672530 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-03-04 | criteria provided, single submitter | clinical testing | The p.E2172D variant (also known as c.6516G>C), located in coding exon 15 of the APC gene, results from a G to C substitution at nucleotide position 6516. The glutamic acid at codon 2172 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is well 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. |
| Invitae | RCV003744564 | SCV002141800 | uncertain significance | Familial adenomatous polyposis 1 | 2023-09-26 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 2172 of the APC protein (p.Glu2172Asp). 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: 485105). 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. |
| Baylor Genetics | RCV003459375 | SCV004191550 | uncertain significance | Familial adenomatous polyposis 1 | 2023-09-06 | criteria provided, single submitter | clinical testing |