ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.1069C>A (p.Pro357Thr) (rs876661264)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000221425 SCV000279923 uncertain significance not provided 2016-02-22 criteria provided, single submitter clinical testing The P357T variant in the PTEN gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P357T variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P357T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret P357T as a variant of uncertain significance.
Invitae RCV000231001 SCV000284579 uncertain significance PTEN hamartoma tumor syndrome 2017-11-13 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 357 of the PTEN protein (p.Pro357Thr). The proline residue is moderately conserved and there is a small physicochemical difference between proline and threonine. 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. ClinVar contains an entry for this variant (Variation ID: 234861). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV000573110 SCV000671726 uncertain significance Hereditary cancer-predisposing syndrome 2016-08-31 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Counsyl RCV000663026 SCV000786053 uncertain significance Cowden syndrome 1 2018-02-12 criteria provided, single submitter clinical testing

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