ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.76A>C (p.Thr26Pro) (rs876661010)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000217854 SCV000279162 likely pathogenic not provided 2016-01-18 criteria provided, single submitter clinical testing This variant is denoted PTEN c.76A>C at the cDNA level, p.Thr26Pro (T26P) at the protein level, and results in the change of a Threonine to a Proline (ACC>CCC). This variant has been observed as a de novo alteration in a 19-year-old female with macrocephaly, goiter, and Lhermitte-Duclos disease, and has also been reported in at least two other individuals with features of Cowden syndrome (Sarquis 2006, Tan 2011, Pilarski 2011, Mester 2012). PTEN Thr26Pro 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 Threonine and Proline differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. PTEN Thr26Pro occurs at a position that is conserved across species and is located in the phosphatase domain (Nguyen 2013). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on the currently available evidence, we consider PTEN Thr26Pro to be a likely pathogenic variant.

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