Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000566035 | SCV000667431 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-10-25 | criteria provided, single submitter | clinical testing | The p.G253C variant (also known as c.757G>T), located in coding exon 7 of the APC gene, results from a G to T substitution at nucleotide position 757. The glycine at codon 253 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not 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. |
Color Diagnostics, |
RCV000566035 | SCV001351794 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-30 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002528038 | SCV002302006 | uncertain significance | Familial adenomatous polyposis 1 | 2022-10-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 253 of the APC protein (p.Gly253Cys). 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: 482278). 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. |
Sema4, |
RCV000566035 | SCV002528204 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-01 | criteria provided, single submitter | curation | |
Baylor Genetics | RCV002528038 | SCV004192060 | uncertain significance | Familial adenomatous polyposis 1 | 2023-09-04 | criteria provided, single submitter | clinical testing |