Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000573197 | SCV000676330 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-07-08 | criteria provided, single submitter | clinical testing | The p.A59T variant (also known as c.175G>A), located in coding exon 2 of the APC gene, results from a G to A substitution at nucleotide position 175. The alanine at codon 59 is replaced by threonine, an amino acid with 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. |
| Invitae | RCV003744576 | SCV002270319 | uncertain significance | Familial adenomatous polyposis 1 | 2021-10-13 | criteria provided, single submitter | clinical testing | 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 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. ClinVar contains an entry for this variant (Variation ID: 487024). 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). This sequence change replaces alanine with threonine at codon 59 of the APC protein (p.Ala59Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. |
| Sema4, |
RCV000573197 | SCV002529751 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-21 | criteria provided, single submitter | curation | |
| Baylor Genetics | RCV003459410 | SCV004197575 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-27 | criteria provided, single submitter | clinical testing |