Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001327848 | SCV001518940 | pathogenic | Tumor predisposition syndrome 3 | 2024-01-04 | 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. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. 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: 1027277). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 10 and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002447383 | SCV002682185 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-17 | criteria provided, single submitter | clinical testing | The c.869+4delA intronic variant is located 4 nucleotides after coding exon 6 of the POT1 gene. This variant results from a deletion of one nucleotide at position c.869+4. This nucleotide position is highly conserved in available vertebrate species. In addition, in silico splice site analysis predicts that this alteration will weaken the native splice donor 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. |