Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000652214 | SCV000774082 | uncertain significance | Tumor predisposition syndrome 3 | 2023-12-16 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 395 of the POT1 protein (p.Gly395Ser). This variant is present in population databases (rs757373061, gnomAD 0.003%). This missense change has been observed in individual(s) with brain oligodendroglioma (PMID: 34193977). ClinVar contains an entry for this variant (Variation ID: 541870). 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. |
Ambry Genetics | RCV001010080 | SCV001170228 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-03 | criteria provided, single submitter | clinical testing | The p.G395S variant (also known as c.1183G>A), located in coding exon 10 of the POT1 gene, results from a G to A substitution at nucleotide position 1183. The glycine at codon 395 is replaced by serine, an amino acid with similar properties. This amino acid position is poorly 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. |
Institute for Clinical Genetics, |
RCV003237976 | SCV002011637 | uncertain significance | not provided | 2021-11-03 | criteria provided, single submitter | clinical testing | |
Center for Genomic Medicine, |
RCV002268237 | SCV002550098 | uncertain significance | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002493048 | SCV002779402 | uncertain significance | Tumor predisposition syndrome 3; Glioma susceptibility 9 | 2022-05-24 | criteria provided, single submitter | clinical testing |