Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV001186350 | SCV001352743 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-01-04 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003537511 | SCV002109273 | uncertain significance | Familial adenomatous polyposis 1 | 2024-01-09 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2122 of the APC protein (p.Ala2122Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with colorectal cancer (PMID: 30093976). ClinVar contains an entry for this variant (Variation ID: 924764). 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. |