Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV004567486 | SCV000261911 | uncertain significance | Familial adenomatous polyposis 1 | 2024-10-31 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 925 of the APC protein (p.Ser925Arg). This variant is present in population databases (no rsID available, 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: 220939). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |
| Ambry Genetics | RCV000566286 | SCV000667471 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-11-20 | criteria provided, single submitter | clinical testing | The p.S925R variant (also known as c.2775C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 2775. The serine at codon 925 is replaced by arginine, an amino acid with dissimilar properties. 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. Missense alterations in APC are not a common cause of disease (Spier I et al. Genet Med. 2024 Feb;26(2):100992). Based on the available evidence, the clinical significance of this variant remains unclear. |
| Color Diagnostics, |
RCV000566286 | SCV000681549 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-23 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with arginine at codon 925 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 hereditary cancer in the literature. This variant has been identified in 1/31414 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 |
RCV002274975 | SCV002562714 | uncertain significance | not provided | 2022-02-14 | 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 |