Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002042789 | SCV002287601 | uncertain significance | Tumor predisposition syndrome 3 | 2023-02-06 | 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: 1501350). This variant has not been reported in the literature in individuals affected with POT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 46 of the POT1 protein (p.Val46Phe). |
| Ambry Genetics | RCV004046009 | SCV005026950 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-23 | criteria provided, single submitter | clinical testing | The p.V46F variant (also known as c.136G>T), located in coding exon 3 of the POT1 gene, results from a G to T substitution at nucleotide position 136. The valine at codon 46 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |