ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.376G>A (p.Ala126Thr) (rs1554898129)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000526114 SCV000645575 uncertain significance PTEN hamartoma tumor syndrome 2017-03-01 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 126 of the PTEN protein (p.Ala126Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual undergoing testing for PTEN-related conditions (PMID: 21659347). An experimental study has shown that this missense change alters substrate specificity of the PTEN phosphatase, resulting in increased Akt signaling (PMID: 26504226). In summary, this variant is a rare missense change that disrupts protein function. While it is absent from the population and reported in affected individuals, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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