Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002035616 | SCV002278228 | uncertain significance | Tumor predisposition syndrome 3 | 2021-05-17 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine with tyrosine at codon 8 of the POT1 protein (p.Asn8Tyr). The asparagine residue is weakly conserved and there is a large physicochemical difference between asparagine and tyrosine. 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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with POT1-related conditions. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV004045934 | SCV005026905 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-09 | criteria provided, single submitter | clinical testing | The p.N8Y variant (also known as c.22A>T), located in coding exon 2 of the POT1 gene, results from an A to T substitution at nucleotide position 22. The asparagine at codon 8 is replaced by tyrosine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |