Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000220589 | SCV000274364 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-24 | criteria provided, single submitter | clinical testing | The p.K1437R variant (also known as c.4310A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 4310. The lysine at codon 1437 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly 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 | RCV003650479 | SCV000552570 | uncertain significance | Familial adenomatous polyposis 1 | 2024-01-20 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 1437 of the APC protein (p.Lys1437Arg). This variant is present in population databases (rs745825088, gnomAD 0.004%). 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: 230719). 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. |
| Mendelics | RCV000463670 | SCV000838114 | uncertain significance | Familial adenomatous polyposis 1 | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000220589 | SCV000911517 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-07 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with arginine at codon 1437 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 APC-related disorders in the literature. This variant has been identified in 4/251050 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. |
| Gene |
RCV001785522 | SCV002028261 | uncertain significance | not provided | 2023-01-11 | criteria provided, single submitter | clinical testing | Not observed at a 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; This variant is associated with the following publications: (PMID: 18199528) |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001785522 | SCV002046429 | uncertain significance | not provided | 2022-12-03 | criteria provided, single submitter | clinical testing | To the best of our knowledge, the variant has not been reported in the published literature. The frequency of this variant in the general population, 0.000026 (3/113452 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |
| Center for Genomic Medicine, |
RCV003320610 | SCV004025060 | benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000463670 | SCV004195122 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-31 | criteria provided, single submitter | clinical testing |