Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000218514 | SCV000273817 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-11-17 | criteria provided, single submitter | clinical testing | The p.P1427A variant (also known as c.4279C>G), located in coding exon 15 of the APC gene, results from a C to G substitution at nucleotide position 4279. The proline at codon 1427 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV003534504 | SCV000814020 | uncertain significance | Familial adenomatous polyposis 1 | 2022-07-29 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 230312). This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1427 of the APC protein (p.Pro1427Ala). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
| Color Diagnostics, |
RCV000218514 | SCV001339987 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-04 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with alanine at codon 1427 of the APC protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on protein structure and function. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with hereditary cancer 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. |
| Gene |
RCV001775678 | SCV002012957 | uncertain significance | not provided | 2019-10-01 | criteria provided, single submitter | clinical testing | Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001797678 | SCV002041528 | uncertain significance | not specified | 2021-11-30 | criteria provided, single submitter | clinical testing |