Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000484715 | SCV000567850 | uncertain significance | not provided | 2022-06-29 | 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 |
| Invitae | RCV003743738 | SCV000647651 | uncertain significance | Familial adenomatous polyposis 1 | 2023-08-16 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with APC-related conditions. This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 2184 of the APC protein (p.Glu2184Lys). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 419788). 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. 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. |
| Ambry Genetics | RCV000561591 | SCV000667473 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-12 | criteria provided, single submitter | clinical testing | The p.E2184K variant (also known as c.6550G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 6550. The glutamic acid at codon 2184 is replaced by lysine, an amino acid with similar properties. This amino acid position is well 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. |
| Color Diagnostics, |
RCV000561591 | SCV001736173 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-28 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with lysine at codon 2184 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported 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. |
| Baylor Genetics | RCV002526552 | SCV004191584 | uncertain significance | Familial adenomatous polyposis 1 | 2023-09-05 | criteria provided, single submitter | clinical testing |