Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000215258 | SCV000277391 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-03 | criteria provided, single submitter | clinical testing | The p.E2463A variant (also known as c.7388A>C), located in coding exon 15 of the APC gene, results from an A to C substitution at nucleotide position 7388. The glutamic acid at codon 2463 is replaced by alanine, an amino acid with dissimilar 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV004563200 | SCV000828797 | uncertain significance | Familial adenomatous polyposis 1 | 2024-04-30 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 2463 of the APC protein (p.Glu2463Ala). 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: 233086). 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 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. |
| All of Us Research Program, |
RCV003998025 | SCV004837234 | uncertain significance | Classic or attenuated familial adenomatous polyposis | 2024-02-05 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with alanine at codon 2463 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. |
| Baylor Genetics | RCV004563200 | SCV005052195 | uncertain significance | Familial adenomatous polyposis 1 | 2024-03-04 | criteria provided, single submitter | clinical testing |