Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001228458 | SCV001400858 | uncertain significance | Tumor predisposition syndrome 3 | 2019-10-25 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine with threonine at codon 177 of the POT1 protein (p.Ala177Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with POT1-related conditions. 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, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
| Ambry Genetics | RCV002348770 | SCV002647184 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-13 | criteria provided, single submitter | clinical testing | The p.A177T variant (also known as c.529G>A), located in coding exon 4 of the POT1 gene, results from a G to A substitution at nucleotide position 529. The alanine at codon 177 is replaced by threonine, an amino acid with similar properties. This amino acid position is conserved. 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. |