Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002230608 | SCV000552758 | uncertain significance | Familial adenomatous polyposis 1 | 2023-08-24 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 411552). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 1916 of the APC protein (p.Gln1916Lys). 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. |
| Ambry Genetics | RCV002348335 | SCV002651634 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-04 | criteria provided, single submitter | clinical testing | The p.Q1916K variant (also known as c.5746C>A), located in coding exon 15 of the APC gene, results from a C to A substitution at nucleotide position 5746. The glutamine at codon 1916 is replaced by lysine, an amino acid with similar properties. In a study aimed at identifying APC variants associated with increased risk of developing colorectal adenomas, the p.Q1916K variant was detected in 0/691 affected individuals and 1/969 healthy controls (Azzopardi D et al. Cancer Res. 2008 Jan;68:358-63). This amino acid position is poorly 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. |