Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000580830 | SCV000681926 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-15 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with leucine at codon 2799 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 not been identified 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. |
Invitae | RCV003653186 | SCV001222880 | uncertain significance | Familial adenomatous polyposis 1 | 2022-11-08 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 489506). This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 2799 of the APC protein (p.Ser2799Leu). |
Gene |
RCV001799689 | SCV002044195 | uncertain significance | not provided | 2021-06-25 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (Lek et al., 2016); 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: 27535533, 18199528) |
Ambry Genetics | RCV000580830 | SCV002677918 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-09-25 | criteria provided, single submitter | clinical testing | The p.S2799L variant (also known as c.8396C>T), located in coding exon 15 of the APC gene, results from a C to T substitution at nucleotide position 8396. The serine at codon 2799 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is 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. |
3DMed Clinical Laboratory Inc | RCV000677762 | SCV000803918 | uncertain significance | Neoplasm of the liver | 2017-08-28 | no assertion criteria provided | clinical testing |