Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001219716 | SCV001391666 | uncertain significance | Tumor predisposition syndrome 3 | 2024-03-20 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 300 of the POT1 protein (p.Asn300Tyr). This variant is present in population databases (rs774946163, gnomAD 0.01%). 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: 948458). 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 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. |
| St. |
RCV001219716 | SCV002584636 | uncertain significance | Tumor predisposition syndrome 3 | 2022-09-09 | criteria provided, single submitter | clinical testing | The POT1 c.898A>T (p.Asn300Tyr) missense change has a maximum subpopulation frequency of 0.012% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with POT1-associated conditions. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
| Ambry Genetics | RCV003294058 | SCV003995288 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-30 | criteria provided, single submitter | clinical testing | The p.N300Y variant (also known as c.898A>T), located in coding exon 7 of the POT1 gene, results from an A to T substitution at nucleotide position 898. The asparagine at codon 300 is replaced by tyrosine, an amino acid with dissimilar 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. |