Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV004574183 | SCV004385861 | uncertain significance | Familial adenomatous polyposis 1 | 2023-03-19 | 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. 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. 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 threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 2495 of the APC protein (p.Thr2495Ala). |
| Ambry Genetics | RCV004943133 | SCV005466824 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-16 | criteria provided, single submitter | clinical testing | The p.T2495A variant (also known as c.7483A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 7483. The threonine at codon 2495 is replaced by alanine, an amino acid with similar properties. This amino acid position is conserved. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Based on the available evidence, the clinical significance of this variant remains unclear. |