Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000817394 | SCV000957950 | uncertain significance | Tumor predisposition syndrome 3 | 2021-04-28 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with phenylalanine at codon 387 of the POT1 protein (p.Leu387Phe). The leucine residue is weakly conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with POT1-related disease. 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. 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 | RCV002352438 | SCV002621113 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-30 | criteria provided, single submitter | clinical testing | The p.L387F variant (also known as c.1161G>T), located in coding exon 9 of the POT1 gene, results from a G to T substitution at nucleotide position 1161. The leucine at codon 387 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is poorly 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. |