Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003766584 | SCV000552662 | uncertain significance | Familial adenomatous polyposis 1 | 2023-09-15 | criteria provided, single submitter | clinical testing | 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. This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 4 of the APC protein (p.Ala4Pro). This variant is present in population databases (rs774219012, gnomAD 0.006%). 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: 411481). 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 | RCV001017299 | SCV001178362 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-26 | criteria provided, single submitter | clinical testing | The p.A4P variant (also known as c.10G>C), located in coding exon 1 of the APC gene, results from a G to C substitution at nucleotide position 10. The alanine at codon 4 is replaced by proline, an amino acid with highly similar properties. This amino acid position is highly 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, |
RCV001017299 | SCV001353778 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-30 | criteria provided, single submitter | clinical testing | This missense variant replaces alanine with proline at codon 4 of the APC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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 been identified in 1/251352 chromosomes 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. |
| Gene |
RCV001753908 | SCV002006771 | uncertain significance | not provided | 2023-11-08 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| 3DMed Clinical Laboratory Inc | RCV000677758 | SCV000803914 | uncertain significance | Carcinoma of colon | 2017-08-11 | no assertion criteria provided | clinical testing |