Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003744665 | SCV000958328 | uncertain significance | Familial adenomatous polyposis 1 | 2022-02-21 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 660533). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is present in population databases (rs759662717, gnomAD 0.003%). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 129 of the APC protein (p.Glu129Gly). |
Color Diagnostics, |
RCV001191301 | SCV001359059 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-30 | criteria provided, single submitter | clinical testing | |
St. |
RCV002535457 | SCV004031123 | uncertain significance | Familial adenomatous polyposis 1 | 2023-08-17 | criteria provided, single submitter | clinical testing | The APC c.386A>G (p.Glu129Gly) missense change has a maximum subpopulation frequency of 0.0033% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, however this prediction is not considered informative for missense variants affecting the APC gene. To our knowledge functional studies have not been performed and this variant has not been reported in individuals with APC-related familial adenomatous polyposis or attenuated familial adenomatous polyposis. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |