Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001242986 | SCV001416114 | pathogenic | PTEN hamartoma tumor syndrome | 2019-09-30 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the PTEN gene (p.Ser338Phefs*6). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 66 amino acids of the PTEN protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PTEN-related conditions. For these reasons, this variant has been classified as Pathogenic. This variant is expected to result in the disruption of the last 66 amino acids (Ser338-Val403) of the PTEN protein. This removes the entire C-tail domain and PDZ binding domain (PMID: 25448482, 25336918, 24905788). This variant also deletes several critical phosphorylation sites within the C-tail domain, which are important for regulating PTEN protein stability and function (PMID: 12297295, 10866658, 11035045, 10468583). No functional studies have been performed to test the effects of this particular variant on PTEN protein stability, cellular location, or function. However, experimental studies have shown that other C-terminal truncating variants in this region affect the stability and function of the PTEN protein (PMID: 10468583, 10698513, 24905788), suggesting that deletion of this region of the PTEN protein is causative of disease. |