Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003767032 | SCV000647602 | uncertain significance | Familial adenomatous polyposis 1 | 2023-08-17 | 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 sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 1879 of the APC protein (p.Ala1879Pro). This variant is present in population databases (rs587779799, gnomAD 0.0009%). 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: 470015). |
| Ambry Genetics | RCV000566961 | SCV000667354 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-16 | criteria provided, single submitter | clinical testing | The p.A1879P variant (also known as c.5635G>C), located in coding exon 15 of the APC gene, results from a G to C substitution at nucleotide position 5635. The alanine at codon 1879 is replaced by proline, an amino acid with highly similar properties. This variant has been reported in 1/1120 pediatric cancer patients who underwent whole genome sequencing and/or whole exome sequencing; this patient was diagnosed with BCR-ABL1 ALL (Zhang J et al. N Engl J Med, 2015 Dec;373:2336-2346). This amino acid position is 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. |