Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000772707 | SCV000905966 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-31 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003653287 | SCV002189143 | uncertain significance | Familial adenomatous polyposis 1 | 2023-09-04 | 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. This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1993 of the APC protein (p.Pro1993Arg). This variant is not present in population databases (gnomAD no frequency). 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: 628291). 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. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). |
| Ambry Genetics | RCV000772707 | SCV002658370 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-30 | criteria provided, single submitter | clinical testing | The p.P1993R variant (also known as c.5978C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 5978. The proline at codon 1993 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. |
| Gene |
RCV003236841 | SCV003935795 | uncertain significance | not provided | 2022-12-22 | 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; This variant is associated with the following publications: (PMID: 18199528) |