Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000235395 | SCV000294054 | uncertain significance | not provided | 2023-09-28 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 18199528, 34371384, 29684080) |
Ambry Genetics | RCV000565628 | SCV000667308 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-17 | criteria provided, single submitter | clinical testing | The p.G2677S variant (also known as c.8029G>A), located in coding exon 15 of the APC gene, results from a G to A substitution at nucleotide position 8029. The glycine at codon 2677 is replaced by serine, an amino acid with similar properties. In a study of whole-exome sequencing in patients with features of Cowden syndrome (CS) or Bannayan-Riley-Ruvalcaba syndrome (BRRS) and negative PTEN testing, this alteration was identified in 0/87 patients with CS or BRRS and 1/3476 patients from The Cancer Genome Atlas (TCGA) (Yehia L et al. PLoS Genet, 2018 04;14:e1007352). 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. |
Color Diagnostics, |
RCV000565628 | SCV000687161 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-19 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003535666 | SCV000833721 | uncertain significance | Familial adenomatous polyposis 1 | 2023-09-08 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2677 of the APC protein (p.Gly2677Ser). This variant is present in population databases (rs750174880, gnomAD 0.0009%). 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: 246482). 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, |
RCV000565628 | SCV002531481 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-13 | criteria provided, single submitter | curation | |
Baylor Genetics | RCV002518467 | SCV004209709 | uncertain significance | Familial adenomatous polyposis 1 | 2023-08-21 | criteria provided, single submitter | clinical testing |