Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003651948 | SCV000647247 | uncertain significance | Familial adenomatous polyposis 1 | 2023-04-11 | 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: 469757). 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 glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 859 of the APC protein (p.Gly859Arg). |
| Ambry Genetics | RCV000564663 | SCV000667731 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-11-23 | criteria provided, single submitter | clinical testing | The p.G859R variant (also known as c.2575G>C), located in coding exon 15 of the APC gene, results from a G to C substitution at nucleotide position 2575. The glycine at codon 859 is replaced by arginine, an amino acid with dissimilar properties. 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. |
| Color Diagnostics, |
RCV000564663 | SCV000681535 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-26 | criteria provided, single submitter | clinical testing | This missense variant replaces glycine with arginine at codon 859 of the APC protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on protein structure and function. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| St. |
RCV000529203 | SCV001737467 | uncertain significance | Familial adenomatous polyposis 1 | 2021-05-13 | criteria provided, single submitter | clinical testing | The APC c.2575G>C (p.Gly859Arg) missense change is absent in gnomAD v2.1.1 (PM2_supporting; https://gnomad.broadinstitute.org/). Six of seven in silico tools predict a benign effect of this variant on protein function, but to our knowledge these predictions have not been confirmed by functional assays. To our knowledge, this variant has not been reported in individuals with familial adenomatous polyposis. In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PM2_supporting. |
| Gene |
RCV002509429 | SCV002818793 | uncertain significance | not provided | 2022-12-28 | 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 |