Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001243894 | SCV001417081 | likely pathogenic | PTEN hamartoma tumor syndrome | 2023-04-24 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with PTEN-related conditions. 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. This variant disrupts the c.253+5G nucleotide in the PTEN gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 24375884, 28677221; Invitae). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. 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 4 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: 968699). This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 4 of the PTEN gene. It does not directly change the encoded amino acid sequence of the PTEN protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. |