Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000546938 | SCV000655189 | uncertain significance | Tumor predisposition syndrome 3 | 2023-09-21 | 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. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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: 475085). This variant has not been reported in the literature in individuals affected with POT1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.002%). This sequence change replaces lysine, which is basic and polar, with arginine, which is basic and polar, at codon 171 of the POT1 protein (p.Lys171Arg). |
| Ambry Genetics | RCV001023587 | SCV001185489 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-05 | criteria provided, single submitter | clinical testing | The p.K171R variant (also known as c.512A>G), located in coding exon 4 of the POT1 gene, results from an A to G substitution at nucleotide position 512. The lysine at codon 171 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is highly 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. |
| Gene |
RCV003148788 | SCV003836924 | uncertain significance | not provided | 2023-03-02 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 28393830) |