Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001012650 | SCV001173129 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-29 | criteria provided, single submitter | clinical testing | The p.V557I variant (also known as c.1669G>A), located in coding exon 13 of the APC gene, results from a G to A substitution at nucleotide position 1669. The valine at codon 557 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is 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 | RCV003744695 | SCV002156729 | uncertain significance | Familial adenomatous polyposis 1 | 2021-10-06 | criteria provided, single submitter | clinical testing | 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. ClinVar contains an entry for this variant (Variation ID: 819784). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with isoleucine at codon 557 of the APC protein (p.Val557Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. 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. |