Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000705781 | SCV000834796 | uncertain significance | Tumor predisposition syndrome 3 | 2021-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with glycine at codon 410 of the POT1 protein (p.Asp410Gly). The aspartic acid residue is moderately conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with POT1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | RCV002360827 | SCV002666190 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-04 | criteria provided, single submitter | clinical testing | The p.D410G variant (also known as c.1229A>G), located in coding exon 10 of the POT1 gene, results from an A to G substitution at nucleotide position 1229. The aspartic acid at codon 410 is replaced by glycine, 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. |