ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.48T>G (p.Tyr16Ter) (rs587782187)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000645066 SCV000766807 pathogenic PTEN hamartoma tumor syndrome 2018-04-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr16*) 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 not been reported in the literature in individuals with PTEN-related disease. A different variant (c.48T>A) giving rise to the same protein effect observed here (p.Tyr16*) has been reported in individuals affected with Cowden Syndrome and Bannayan-Riley-Ruvalcaba Syndrome (PMID: 16773562, 21194675). Loss-of-function variants in PTEN are known to be pathogenic (PMID: 9467011, 21194675). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000645066 SCV000967758 pathogenic PTEN hamartoma tumor syndrome 2018-04-27 criteria provided, single submitter clinical testing The p.Tyr16X variant in PTEN has been reported as a consequence of at least 4 di fferent cDNA changes and is present in ClinVar (c.48T>G, c.48T>A: ID# 142027, c. 48_49delinsAT, or c.47dupA: ID# 234409). The c.48T>G variant, identified in this individual, has not been previously reported in individuals with PTEN-associate d conditions but the available data from the other changes supports pathogenicit y: Collectively, the p.Tyr16X variant has been reported in at least 6 individual s with phenotypes consistent PTEN hamartoma tumor syndrome (PHTS) (c.48T>A: 2 in dividuals with Cowden syndrome (SC) (Tan 2011); c.48_49delinsAT: 1 individual wi th CS and 1 individual with Bannayan-Riley-Ruvalcaba syndrome (BRRS) (Sarquis 20 06); c.47dupA: 1 individual with CS or CS-like syndrome with hyperplastic polyp s in the upper gastrointestinal tract (Zbuk 2007, Ngeow 2011, Head 2010); p.Tyr1 6X (cDNA change unspecified: 1 individual with adult Lhermitte-Duclos disease (L DD) and clinical features of Cowden (Zhou 2003)). All changes leading to the pTy r16X variant are absent from large population studies. This variant represents a premature termination codon at position 16, which is predicted to lead to a tru ncated or absent protein. Heterozygous loss of function of the PTEN gene is an e stablished disease mechanism in PTEN-associated conditions. In summary, the p.Ty r16X variant meets criteria to be classified as pathogenic for PTEN-associated c onditions in an autosomal dominant manner based upon absence from controls, pred icted impact on the protein, and presence in affected individuals. ACMG/AMP Crit eria applied: PVS1, PM2, PS4_moderate.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001195980 SCV001366407 pathogenic Megalencephaly; Global developmental delay; Seizures; Macrocephalus; Colpocephaly 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PM2,PP3,PP4. This variant was detected in heterozygous state.

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