ClinVar Miner

Submissions for variant NM_000314.8(PTEN):c.1168G>T (p.Glu390Ter)

dbSNP: rs2132290171
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001377580 SCV001574950 likely pathogenic PTEN hamartoma tumor syndrome 2022-12-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu390*) in the PTEN gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 14 amino acid(s) of the PTEN protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PTEN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1066560). This variant disrupts the C-tail domain and PDZ binding domain of the PTEN protein (PMID: 25448482, 25336918, 24905788) and several critical phosphorylation sites within the C-tail domain, which are important for regulating PTEN protein stability and function (PMID: 12297295, 10866658, 11035045, 10468583). While functional studies have not been performed to directly test the effect of this variant on PTEN protein function, this suggests that disruption of this region of the protein is causative of disease. 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.
GeneDx RCV003235568 SCV003932933 uncertain significance not provided 2024-09-30 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation as the last 14 amino acids are lost with an unclear effect on protein function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 18626510)

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