Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000217057 | SCV000274512 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-31 | criteria provided, single submitter | clinical testing | The p.Q445E variant (also known as c.1333C>G), located in coding exon 10 of the APC gene, results from a C to G substitution at nucleotide position 1333. The glutamine at codon 445 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is highly 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. |
| Ce |
RCV000585258 | SCV000693182 | uncertain significance | not provided | 2017-10-01 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000585258 | SCV000693993 | uncertain significance | not provided | 2017-06-05 | criteria provided, single submitter | clinical testing | Variant summary: The APC c.1333C>G (p.Gln445Glu) variant causes a missense change involving the alteration of a conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPsandGO not captured due to low reliability index). The variant of interest is absent in a large, broad control population, ExAC in 120462 control chromosomes. In addition, one clinical diagnostic laboratory classified this variant as uncertain significance. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS). |
| Color Diagnostics, |
RCV000217057 | SCV000904772 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-16 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003475011 | SCV001374523 | uncertain significance | Familial adenomatous polyposis 1 | 2023-12-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 445 of the APC protein (p.Gln445Glu). 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: 230838). 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. |
| Fulgent Genetics, |
RCV002494587 | SCV002802058 | uncertain significance | Desmoid disease, hereditary; Familial adenomatous polyposis 1; Hepatocellular carcinoma; Gastric cancer; Colorectal cancer; Gastric adenocarcinoma and proximal polyposis of the stomach | 2022-05-14 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003475011 | SCV004202659 | uncertain significance | Familial adenomatous polyposis 1 | 2023-08-09 | criteria provided, single submitter | clinical testing |