Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003766567 | SCV000552556 | uncertain significance | Familial adenomatous polyposis 1 | 2023-07-08 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 2185 of the APC protein (p.Ser2185Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with gallbladder and pancreatic cancer (PMID: 30093976). ClinVar contains an entry for this variant (Variation ID: 411410). 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. 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 | RCV002365659 | SCV002663470 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-03 | criteria provided, single submitter | clinical testing | The p.S2185G variant (also known as c.6553A>G), located in coding exon 15 of the APC gene, results from an A to G substitution at nucleotide position 6553. The serine at codon 2185 is replaced by glycine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. This alteration was reported in a cohort of Asian patients with multiple primary cancer diagnoses undergoing multigene panel testing for hereditary cancer susceptibility (Chan GHJ et al. Oncotarget. 2018 Jul;9:30649-30660). 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. |
| 3DMed Clinical Laboratory Inc | RCV000677772 | SCV000803928 | uncertain significance | Malignant tumor of ascending colon | 2017-12-14 | no assertion criteria provided | clinical testing |