Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV004561579 | SCV000647455 | uncertain significance | Familial adenomatous polyposis 1 | 2022-03-11 | criteria provided, single submitter | clinical testing | 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: 469926). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1188 of the APC protein (p.Pro1188Thr). |
| Ambry Genetics | RCV002456176 | SCV002613882 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-10 | criteria provided, single submitter | clinical testing | The p.P1188T variant (also known as c.3562C>A), located in coding exon 15 of the APC gene, results from a C to A substitution at nucleotide position 3562. The proline at codon 1188 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is not well 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. |