Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV004572198 | SCV002589957 | uncertain significance | Familial adenomatous polyposis 1 | 2022-09-23 | 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. This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 565 of the APC protein (p.Glu565Asp). 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. 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. |
| Ambry Genetics | RCV003164516 | SCV003866297 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-16 | criteria provided, single submitter | clinical testing | The p.E565D variant (also known as c.1695A>C), located in coding exon 13 of the APC gene, results from an A to C substitution at nucleotide position 1695. The glutamic acid at codon 565 is replaced by aspartic acid, 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. |