Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003535887 | SCV000936877 | uncertain significance | Familial adenomatous polyposis 1 | 2021-09-19 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with proline at codon 281 of the APC protein (p.Thr281Pro). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and proline. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with APC-related conditions. This variant is not present in population databases (ExAC no frequency). |
Revvity Omics, |
RCV003141784 | SCV003826837 | uncertain significance | not provided | 2022-11-10 | criteria provided, single submitter | clinical testing | |
Gene |
RCV003141784 | SCV003837231 | uncertain significance | not provided | 2022-08-29 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV003166154 | SCV003866311 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-28 | criteria provided, single submitter | clinical testing | The p.T281P variant (also known as c.841A>C), located in coding exon 8 of the APC gene, results from an A to C substitution at nucleotide position 841. The threonine at codon 281 is replaced by proline, an amino acid with highly similar properties. This amino acid position is not well 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. |