Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000204328 | SCV000259303 | uncertain significance | Familial adenomatous polyposis 1 | 2023-12-19 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 881 of the APC protein (p.Ser881Phe). This variant is present in population databases (rs535344579, gnomAD 0.007%). 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: 219437). 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 |
RCV000478187 | SCV000572228 | uncertain significance | not provided | 2021-05-27 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at a significant frequency in large population cohorts (Lek 2016) |
| Ambry Genetics | RCV000565056 | SCV000675876 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-12 | criteria provided, single submitter | clinical testing | The p.S881F variant (also known as c.2642C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 2642. The serine at codon 881 is replaced by phenylalanine, an amino acid with highly dissimilar properties. In one study, this variant was detected in 0/165 colorectal cancer and/or polyposis patients and was identified in control individual(s) from a healthy population database (Rosenthal EA et al. Hum Genet, 2018 Oct;137:795-806). This amino acid position is not well conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Based on the available evidence, the clinical significance of this alteration remains unclear. |
| Mendelics | RCV003491951 | SCV000838094 | likely benign | Hereditary cancer | 2024-01-23 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000565056 | SCV000904121 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-27 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with phenylalanine at codon 881 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 been identified in 1/31358 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. |
| Baylor Genetics | RCV000204328 | SCV004209620 | uncertain significance | Familial adenomatous polyposis 1 | 2024-03-01 | criteria provided, single submitter | clinical testing |