ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.991_992del (p.Asp331fs) (rs1554825611)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000531694 SCV000645638 pathogenic PTEN hamartoma tumor syndrome 2017-08-10 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the PTEN gene (p.Asp331Glnfs*11). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 73 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 disease. This variant is expected to result in the disruption of the last 73 amino acid residues (Asp331-Val403) of the PTEN protein. This removes the C-terminal portion of the C2 domain, as well as 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 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). This suggests that disruption of this region of the PTEN protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.

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