Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001214258 | SCV001385932 | uncertain significance | Tumor predisposition syndrome 3 | 2023-08-28 | criteria provided, single submitter | clinical testing | 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: 943965). 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 aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 219 of the POT1 protein (p.Asp219Glu). 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 | RCV002365963 | SCV002663357 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-11-25 | criteria provided, single submitter | clinical testing | The p.D219E variant (also known as c.657C>A), located in coding exon 5 of the POT1 gene, results from a C to A substitution at nucleotide position 657. The aspartic acid at codon 219 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |