ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.46T>G (p.Tyr16Asp) (rs1064796078)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000481194 SCV000572492 likely pathogenic not provided 2016-12-23 criteria provided, single submitter clinical testing This variant is denoted PTEN c.46T>G at the cDNA level, p.Tyr16Asp (Y16D) at the protein level, and results in the change of a Tyrosine to an Aspartic Acid (TAT>GAT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. However, PTEN Tyr16Cys has been shown to impact phosphatase activity and cellular localization (Han 2000, Kim 2011, Gil 2015), and PTEN Tyr16His has been observed in an individual with breast and endometrial cancer as well as other findings suggestive of PTEN Hamartoma Tumor syndrome (Ngeow 2014). PTEN Tyr16Asp was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Tyrosine and Aspartic Acid differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. PTEN Tyr16Asp occurs at a position that is conserved across species and is located within the N-terminal nuclear localization signal and the phosphatase domain (Molinari 2014, Gil 2015). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, we consider this variant to be likely pathogenic.

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