Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV004562816 | SCV000964561 | uncertain significance | Familial adenomatous polyposis 1 | 2023-06-19 | 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. ClinVar contains an entry for this variant (Variation ID: 665416). 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 valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 2414 of the APC protein (p.Val2414Ile). |
| Gene |
RCV004773203 | SCV005387285 | uncertain significance | not provided | 2024-02-28 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV004944225 | SCV005465072 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-08-10 | criteria provided, single submitter | clinical testing | The p.V2414I variant (also known as c.7240G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 7240. The valine at codon 2414 is replaced by isoleucine, an amino acid with highly 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. |