Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001992198 | SCV002284086 | uncertain significance | Tumor predisposition syndrome 3 | 2024-08-22 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 622 of the POT1 protein (p.Tyr622Ser). This variant is not present in population databases (gnomAD no frequency). 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: 1497052). 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 | RCV004045514 | SCV005026902 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-01-29 | criteria provided, single submitter | clinical testing | The p.Y622S variant (also known as c.1865A>C), located in coding exon 15 of the POT1 gene, results from an A to C substitution at nucleotide position 1865. The tyrosine at codon 622 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |