Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000693013 | SCV000820866 | uncertain significance | Tumor predisposition syndrome 3 | 2023-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 441 of the POT1 protein (p.Asn441Ser). This variant is present in population databases (no rsID available, gnomAD 0.01%). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt POT1 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. ClinVar contains an entry for this variant (Variation ID: 571778). This variant has not been reported in the literature in individuals affected with POT1-related conditions. |
| Ambry Genetics | RCV001011011 | SCV001171288 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-08 | criteria provided, single submitter | clinical testing | The p.N441S variant (also known as c.1322A>G), located in coding exon 10 of the POT1 gene, results from an A to G substitution at nucleotide position 1322. The asparagine at codon 441 is replaced by serine, 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. |