Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV004573235 | SCV004471866 | uncertain significance | Familial adenomatous polyposis 1 | 2023-04-12 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2135 of the APC protein (p.Ile2135Thr). 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. 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 | RCV004654300 | SCV005153968 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-20 | criteria provided, single submitter | clinical testing | The p.I2135T variant (also known as c.6404T>C), located in coding exon 15 of the APC gene, results from a T to C substitution at nucleotide position 6404. The isoleucine at codon 2135 is replaced by threonine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Based on the available evidence, the clinical significance of this alteration remains unclear. |