Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000549999 | SCV000655192 | uncertain significance | Tumor predisposition syndrome 3 | 2024-11-11 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 193 of the POT1 protein (p.Ser193Pro). This variant is present in population databases (rs752854457, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with POT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 475088). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt POT1 protein function with a negative predictive value of 80%. 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 | RCV002358606 | SCV002648915 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-05-15 | criteria provided, single submitter | clinical testing | The p.S193P variant (also known as c.577T>C), located in coding exon 5 of the POT1 gene, results from a T to C substitution at nucleotide position 577. The serine at codon 193 is replaced by proline, 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. |