ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.379G>A (p.Gly127Arg) (rs587781255)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479167 SCV000568255 likely pathogenic not provided 2016-11-08 criteria provided, single submitter clinical testing This variant is denoted PTEN c.379G>A at the cDNA level, p.Gly127Arg (G127R) at the protein level, and results in the change of a Glycine to an Arginine (GGA>AGA). This variant was observed in several individual that met clinical diagnostic criteria for Cowden syndrome and in an individual with multiple primary malignant tumors (Lachlan 2007, Pal 2012, Whitworth 2015) . Additionally, in vivo tumor formation assays and gene expression profiling performed by Kim et al. (2016) inferred that this variant would exhibit significantly distinct protein expression from wild type. PTEN Gly127Arg 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 Glycine and Arginine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. PTEN Gly127Arg occurs at a position that is conserved across species and is located in ATP binding motif and the phosphatase core domain (Lee 1999, Lobo 2009). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on the currently available evidence, we consider PTEN Gly127Arg to be a likely pathogenic variant.
Medical Molecular Genetics,University of Birmingham RCV000128454 SCV000172155 pathogenic PTEN hamartoma tumor syndrome 2012-08-01 no assertion criteria provided clinical testing Clinically treated as causative

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