Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001017883 | SCV001179047 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-11 | criteria provided, single submitter | clinical testing | The p.S283A variant (also known as c.847T>G), located in coding exon 6 of the POT1 gene, results from a T to G substitution at nucleotide position 847. The serine at codon 283 is replaced by alanine, an amino acid with similar properties. This amino acid position is not well 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. |
| Invitae | RCV001345480 | SCV001539600 | uncertain significance | Tumor predisposition syndrome 3 | 2023-07-07 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 283 of the POT1 protein (p.Ser283Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with POT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 822490). 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. 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. |
| Gene |
RCV001585922 | SCV001812479 | uncertain significance | not provided | 2022-09-29 | criteria provided, single submitter | clinical testing | Not observed 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 |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001585922 | SCV004219111 | uncertain significance | not provided | 2022-09-30 | criteria provided, single submitter | clinical testing | The variant has not been reported in the published literature. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |