ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.892C>T (p.Gln298Ter) (rs371387815)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000167405 SCV000218260 pathogenic Hereditary cancer-predisposing syndrome 2017-10-31 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Other acmg-defined mutation (i.e. initiation codon or gross deletion)
ClinGen PTEN Variant Curation Expert Panel RCV000645029 SCV000840489 pathogenic PTEN hamartoma tumor syndrome 2017-10-18 reviewed by expert panel curation PTEN c.892C>T (p.Q298X) meets criteria to be classified as pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (Mester et al. 2018; manuscript in preparation). Please see a summary of the rules and criteria codes in the 'PTEN ACMG Specifications Summary' document (assertion method column). PVS1: Null variant predicted to result in nonsense-mediated decay or causing truncation/frameshift at or 5' to c.1121 (NM_000314.4). PM2: Absent in large sequenced populations (PMID 27535533). PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (PMID 23470840)
GeneDx RCV000315739 SCV000329756 pathogenic not provided 2018-04-03 criteria provided, single submitter clinical testing The Q298X nonsense variant in the PTEN gene has been reported previously in an individual with a clinical diagnosis of Cowden syndrome (Tan et al., 2011; Busch et al., 2013). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, we interpret Q298X as a pathogenic variant.
Invitae RCV000645029 SCV000766768 pathogenic PTEN hamartoma tumor syndrome 2017-12-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln298*) in the PTEN gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with Cowden or Cowden-like syndrome (PMID: 21194575). ClinVar contains an entry for this variant (Variation ID: 187657). Loss-of-function variants in PTEN are known to be pathogenic (PMID: 9467011, 21194675). For these reasons, this variant has been classified as Pathogenic.

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