Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001025252 | SCV001187405 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-10-19 | criteria provided, single submitter | clinical testing | The p.I2142M variant (also known as c.6426C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 6426. The isoleucine at codon 2142 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV003769607 | SCV002244308 | uncertain significance | Familial adenomatous polyposis 1 | 2024-02-27 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 2142 of the APC protein (p.Ile2142Met). 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. ClinVar contains an entry for this variant (Variation ID: 826395). 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. |
| Prevention |
RCV003393787 | SCV004119632 | uncertain significance | APC-related disorder | 2022-12-07 | criteria provided, single submitter | clinical testing | The APC c.6426C>G variant is predicted to result in the amino acid substitution p.Ile2142Met. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/826395/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |