Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000129389 | SCV000184155 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-29 | criteria provided, single submitter | clinical testing | The p.E2589G variant (also known as c.7766A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 7766. The glutamic acid at codon 2589 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV003650357 | SCV000254039 | uncertain significance | Familial adenomatous polyposis 1 | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 2589 of the APC protein (p.Glu2589Gly). This variant is present in population databases (rs200406572, gnomAD 0.003%). 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: 41515). 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 with a negative predictive value of 95%. 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. |
Gene |
RCV000034400 | SCV000565845 | uncertain significance | not provided | 2023-09-11 | 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; Observed in an individual with atherosclerosis undergoing exome sequencing (Johnston et al., 2012); This variant is associated with the following publications: (PMID: 18199528, 22703879) |
Color Diagnostics, |
RCV000129389 | SCV000687142 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-03 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with glycine at codon 2589 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders in the literature. This variant has been identified in 1/250812 chromosomes 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000034400 | SCV000888767 | uncertain significance | not provided | 2017-10-10 | criteria provided, single submitter | clinical testing | |
Division of Medical Genetics, |
RCV000200515 | SCV001424810 | uncertain significance | Familial adenomatous polyposis 1 | 2019-06-17 | criteria provided, single submitter | clinical testing | To our knowledge, this sequence variant has not been previously reported in the literature in individuals with colon polyps or colon cancer. This variant has an overall allele frequency of 0.000004 in the Broad Institute gnomAD Browser (https://gnomad.broadinstitute.org/). In silico analyses indicate this is an evolutionarily conserved residue. Thus, it is unknown at this time whether this variant increases cancer risk. |
Institute for Clinical Genetics, |
RCV000034400 | SCV002010856 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000200515 | SCV004196356 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-16 | criteria provided, single submitter | clinical testing | |
Biesecker Lab/Clinical Genomics Section, |
RCV000034400 | SCV000043142 | variant of unknown significance | not provided | 2012-07-13 | no assertion criteria provided | research | Converted during submission to Uncertain significance. |