Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001016971 | SCV001177984 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-10-07 | criteria provided, single submitter | clinical testing | The c.1007-2_1009delAGTAC variant results from a deletion of 5 nucleotides between positions c.1007-2 and c.1009 and involves the canonical splice acceptor site before coding exon 9 of the POT1 gene. The canonical splice acceptor site is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may result in the creation or strengthening of a novel splice acceptor site; however, direct evidence is insufficient at this time (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV005093147 | SCV005805699 | likely pathogenic | Tumor predisposition syndrome 3 | 2024-05-08 | criteria provided, single submitter | clinical testing | This variant results in the deletion of part of exon 13 (c.1007-2_1009del) of the POT1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in POT1 are known to be pathogenic (PMID: 32155570). This variant is present in population databases (rs754005964, gnomAD 0.007%). 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: 821995). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |