Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001204292 | SCV001375492 | uncertain significance | Tumor predisposition syndrome 3 | 2023-05-15 | criteria provided, single submitter | clinical testing | 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: 935652). This variant has not been reported in the literature in individuals affected with POT1-related conditions. This variant is present in population databases (rs775892143, gnomAD 0.0009%). This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 498 of the POT1 protein (p.Ile498Met). |
| Gene |
RCV001760165 | SCV001998478 | uncertain significance | not provided | 2019-11-19 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Ambry Genetics | RCV003163543 | SCV003913099 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-23 | criteria provided, single submitter | clinical testing | The p.I498M variant (also known as c.1494A>G), located in coding exon 11 of the POT1 gene, results from an A to G substitution at nucleotide position 1494. The isoleucine at codon 498 is replaced by methionine, an amino acid with highly 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. |