Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001025953 | SCV001188242 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-17 | criteria provided, single submitter | clinical testing | The c.703-3T>G intronic variant results from a T to G substitution 3 nucleotides upstream from coding exon 6 in the POT1 gene. This nucleotide position is well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Invitae | RCV003769619 | SCV004683999 | uncertain significance | Tumor predisposition syndrome 3 | 2023-08-24 | criteria provided, single submitter | clinical testing | 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). 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. ClinVar contains an entry for this variant (Variation ID: 826789). This variant has not been reported in the literature in individuals affected with POT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 9 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. |