Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003650466 | SCV000260979 | uncertain significance | Familial adenomatous polyposis 1 | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 1994 of the APC protein (p.Asp1994Glu). This variant is present in population databases (rs372852823, gnomAD 0.006%). 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: 220442). 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 with a negative predictive value of 95%. 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, |
RCV000775337 | SCV000909608 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-31 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000775337 | SCV001186824 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-23 | criteria provided, single submitter | clinical testing | The p.D1994E variant (also known as c.5982C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 5982. The aspartic acid at codon 1994 is replaced by glutamic acid, an amino acid with highly similar properties. In one study, this variant was detected in 0/165 colorectal cancer and/or polyposis patients and was identified in 1/2512 control individuals from a healthy population database (Rosenthal EA et al. Hum. Genet., 2018 Oct;137:795-806). This amino acid position is not 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. |
| Baylor Genetics | RCV002515525 | SCV004195561 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-23 | criteria provided, single submitter | clinical testing |