Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001016934 | SCV001177943 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-03-18 | criteria provided, single submitter | clinical testing | The p.T97N variant (also known as c.290C>A), located in coding exon 4 of the POT1 gene, results from a C to A substitution at nucleotide position 290. The threonine at codon 97 is replaced by asparagine, an amino acid with 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. |
Invitae | RCV001860848 | SCV002205543 | uncertain significance | Tumor predisposition syndrome 3 | 2022-11-29 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.01%). 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. 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. ClinVar contains an entry for this variant (Variation ID: 821974). This variant has not been reported in the literature in individuals affected with POT1-related conditions. This sequence change replaces threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 97 of the POT1 protein (p.Thr97Asn). |