Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000574779 | SCV000667696 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-10-27 | criteria provided, single submitter | clinical testing | The p.S95F variant (also known as c.284C>T), located in coding exon 3 of the APC gene, results from a C to T substitution at nucleotide position 284. The serine at codon 95 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, in silico predictors for this gene do not accurately predict pathogenicity. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV004561717 | SCV000936712 | uncertain significance | Familial adenomatous polyposis 1 | 2024-04-30 | 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 95 of the APC protein (p.Ser95Phe). 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: 482441). 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 |
RCV001764656 | SCV002008333 | uncertain significance | not provided | 2022-11-22 | criteria provided, single submitter | clinical testing | Not observed 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 |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003114691 | SCV003800702 | uncertain significance | not specified | 2023-01-12 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV004000990 | SCV004826902 | uncertain significance | Classic or attenuated familial adenomatous polyposis | 2023-04-27 | criteria provided, single submitter | clinical testing |