ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.511C>T (p.Gln171Ter) (rs786204864)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PTEN Variant Curation Expert Panel RCV000233297 SCV000840464 pathogenic PTEN hamartoma tumor syndrome 2017-10-18 reviewed by expert panel curation PTEN c.511C>T (p.Q171X) 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). PM6: Assumed de novo, but without confirmation of paternity and maternity in a patient with the disease and no family history. (PMID 22595938) PS4_M: Probands with phenotype specificity score of 2-3.5. (PMID 17043057, PMID 22595938)
GeneDx RCV000169804 SCV000222121 pathogenic not provided 2018-07-19 criteria provided, single submitter clinical testing This variant is denoted PTEN c.511C>T at the cDNA level and p.Gln171Ter (Q171X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in individuals with Cowden syndrome and is considered pathogenic (Suphapeetiporn 2006, Hobert 2012, Chen 2017).
Invitae RCV000233297 SCV000284594 pathogenic PTEN hamartoma tumor syndrome 2019-12-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln171*) 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 observed in a family affected with Bannayan-Riley-Ruvalcaba syndrome (PMID: 17043057) and as de novo in an individual with PTEN hamartoma tumor syndrome (PMID: 22595938). ClinVar contains an entry for this variant (Variation ID: 189411). Experimental studies have demonstrated that this variant may also cause a skipping of exon 6, which is also deleterious (PMID: 17043057). Loss-of-function variants in PTEN are known to be pathogenic (PMID: 9467011, 21194675). For these reasons, this variant has been classified as Pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000169804 SCV000334953 pathogenic not provided 2015-09-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV000491520 SCV000579991 pathogenic Hereditary cancer-predisposing syndrome 2017-09-08 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)

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