Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000222801 | SCV000276357 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-09-13 | criteria provided, single submitter | clinical testing | The p.A1731G variant (also known as c.5192C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 5192. The alanine at codon 1731 is replaced by glycine, an amino acid with similar 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. Based on the available evidence, the clinical significance of this variant remains unclear. |
| Labcorp Genetics |
RCV002519703 | SCV000647562 | uncertain significance | Familial adenomatous polyposis 1 | 2024-09-04 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 1731 of the APC protein (p.Ala1731Gly). 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: 232267). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |
| Baylor Genetics | RCV002519703 | SCV004203891 | uncertain significance | Familial adenomatous polyposis 1 | 2023-07-07 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV003997956 | SCV004831198 | uncertain significance | Classic or attenuated familial adenomatous polyposis | 2023-04-10 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with glycine at codon 1731 of the APC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with APC-related disorders 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. |
| Institute for Biomarker Research, |
RCV000222801 | SCV005045476 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-22 | criteria provided, single submitter | clinical testing |