Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003649272 | SCV001200817 | uncertain significance | Familial adenomatous polyposis 1 | 2022-05-05 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 836305). 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: "Possibly 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. This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 1047 of the APC protein (p.Glu1047Ala). 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. |
| Ambry Genetics | RCV002320238 | SCV002610613 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-03-19 | criteria provided, single submitter | clinical testing | The p.E1047A variant (also known as c.3140A>C), located in coding exon 15 of the APC gene, results from an A to C substitution at nucleotide position 3140. The glutamic acid at codon 1047 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. |