Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001012733 | SCV001173222 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-31 | criteria provided, single submitter | clinical testing | The c.1686+4_1686+7delAGTA intronic variant results from a deletion of 4 nucleotides within intron 13 of the POT1 gene. This nucleotide region is well conserved in available vertebrate species. Using two different splice site prediction tools, this alteration is predicted by ESEfinder to weaken the efficiency of the native splice donor site, but is not predicted to have a deleterious effect on this splice donor site by BDGP; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001325112 | SCV001516090 | uncertain significance | Tumor predisposition syndrome 3 | 2024-11-19 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 17 of the POT1 gene. It does not directly change the encoded amino acid sequence of the POT1 protein. It affects a nucleotide within the consensus splice site. 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: 819836). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus 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. |