Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000556726 | SCV000655130 | uncertain significance | Tumor predisposition syndrome 3 | 2024-01-16 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 405 of the POT1 protein (p.Ala405Thr). This variant is present in population databases (rs753851042, gnomAD 0.006%). 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: 475030). 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 | RCV002358603 | SCV002660044 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-09-12 | criteria provided, single submitter | clinical testing | The p.A405T variant (also known as c.1213G>A), located in coding exon 10 of the POT1 gene, results from a G to A substitution at nucleotide position 1213. The alanine at codon 405 is replaced by threonine, 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. |
Prevention |
RCV003403334 | SCV004104661 | uncertain significance | POT1-related condition | 2022-08-26 | criteria provided, single submitter | clinical testing | The POT1 c.1213G>A variant is predicted to result in the amino acid substitution p.Ala405Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0058% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-124481183-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |