Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000572598 | SCV000674416 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-01-24 | criteria provided, single submitter | clinical testing | The c.870-3T>C intronic variant results from a T to C substitution 3 nucleotides upstream from coding exon 7 in the POT1 gene. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. This nucleotide position is not well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001373990 | SCV001570744 | uncertain significance | Tumor predisposition syndrome 3 | 2023-11-21 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 10 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 present in population databases (no rsID available, gnomAD 0.0009%). 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: 486146). 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 is not likely to affect RNA splicing. 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. |
| Sema4, |
RCV000572598 | SCV002527179 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-14 | criteria provided, single submitter | curation |