Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000614285 | SCV000712776 | uncertain significance | not specified | 2017-01-12 | criteria provided, single submitter | clinical testing | The p.Val198Ile variant in APC has not been previously reported in individuals w ith APC-associated polyposis or in large population studies. Computational predi ction tools and conservation analysis suggest that the p.Val198Ile variant may n ot impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p.Val198Ile vari ant is uncertain. |
| Ambry Genetics | RCV001024694 | SCV001186757 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-28 | criteria provided, single submitter | clinical testing | The p.V198I variant (also known as c.592G>A), located in coding exon 5 of the APC gene, results from a G to A substitution at nucleotide position 592. The valine at codon 198 is replaced by isoleucine, an amino acid with highly similar properties. This alteration was detected in a study of 1,165 individuals with a history of colorectal cancer or colon polyps as well as 590 controls (Gordon AS et al. Am J Hum Genet, 2019 09;105:526-533). This amino acid position is not well 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. |
| Invitae | RCV002529343 | SCV001210841 | uncertain significance | Familial adenomatous polyposis 1 | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with isoleucine at codon 198 of the APC protein (p.Val198Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is not present in population databases (ExAC 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: 505513). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. |