Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000601902 | SCV000731389 | uncertain significance | not specified | 2017-02-20 | criteria provided, single submitter | clinical testing | The p.Val2014Ile variant in APC has not been previously reported in individuals with familial adenomatous polyposis or other APC-associated disorders. This vari ant has been identified in 1/8636 of East Asian chromosomes by the Exome Aggrega tion Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs143313902). Compu tational prediction tools and conservation analysis do not provide strong suppor t for or against an impact to the protein. In summary, the clinical significance of the p.Val2014Ile variant is uncertain. |
| Invitae | RCV003538411 | SCV000832974 | uncertain significance | Familial adenomatous polyposis 1 | 2022-11-28 | 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: 517226). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (rs143313902, gnomAD 0.006%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 2014 of the APC protein (p.Val2014Ile). |
| Ambry Genetics | RCV001024834 | SCV001186920 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-08 | criteria provided, single submitter | clinical testing | The p.V2014I variant (also known as c.6040G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 6040. The valine at codon 2014 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is highly 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. |
| Baylor Genetics | RCV002528768 | SCV004207206 | uncertain significance | Familial adenomatous polyposis 1 | 2023-01-30 | criteria provided, single submitter | clinical testing |