Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001232089 | SCV001404634 | uncertain significance | Tumor predisposition syndrome 3 | 2022-08-09 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 18 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 has not been reported in the literature in individuals affected with POT1-related conditions. 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. 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. ClinVar contains an entry for this variant (Variation ID: 958844). |
| Ambry Genetics | RCV002402726 | SCV002713006 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-07-16 | criteria provided, single submitter | clinical testing | The c.1792+1G>A intronic variant results from a G to A substitution one nucleotide after coding exon 14 of the POT1 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein. As such, this alteration is classified as likely pathogenic. |