ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.395G>A (p.Gly132Asp) (rs121909241)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PTEN Variant Curation Expert Panel RCV000544638 SCV000863470 likely pathogenic PTEN hamartoma tumor syndrome 2018-04-06 reviewed by expert panel curation PTEN c.395G>A (p.G132D) meets criteria to be classified as likely pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the "PTEN ACMG Specifications Summary" document (assertion method column). 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. (Internal laboratory contributor(s) SCV000279163.8) PS4_M: Probands with phenotype specificity score of 2-3.5. (PMID 25288137, PMID 23335809, PMID 23470840, internal laboratory contributor(s)) PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000078616 SCV000110472 uncertain significance not provided 2017-12-07 criteria provided, single submitter clinical testing
GeneDx RCV000078616 SCV000279163 likely pathogenic not provided 2018-06-29 criteria provided, single submitter clinical testing This variant is denoted PTEN c.395G>A at the cDNA level, p.Gly132Asp (G132D) at the protein level, and results in the change of a Glycine to an Aspartic Acid (GGT>GAT). This variant has been reported in several individuals with clinical histories consistent with PTEN hamartoma tumor syndrome (PHTS), including at least two individuals with pathognomonic features of Cowden syndrome (Derrey 2004, Heindl 2012, Busch 2013, Bubien 2013, Frazier 2015). PTEN Gly132Asp was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Glycine and Aspartic Acid differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. PTEN Gly132Asp occurs at a position that is conserved across species and is located within the phosphatase tensin-type domain (Nguyen 2014). In silico analyses predict that this variant is probably damaging to protein structure and function. The currently available information regarding this variant suggests pathogenicity; however functional data examining the effect of this variant on the function of the protein has not been published. We therefore consider PTEN Gly132Asp to be a likely pathogenic variant.
Invitae RCV000544638 SCV000645579 pathogenic PTEN hamartoma tumor syndrome 2019-09-03 criteria provided, single submitter clinical testing This sequence change replaces glycine with aspartic acid at codon 132 of the PTEN protein (p.Gly132Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with PTEN hamartoma tumor syndrome (PMID: 23470840, 22266152, 23335809, 20600018, 27477328). ClinVar contains an entry for this variant (Variation ID: 92822). This variant has been reported to affect PTEN protein function (PMID: 29706350). This variant disrupts the p.Gly132 amino acid residue in PTEN. Other variant(s) that disrupt this residue have been observed in individuals with PTEN-related conditions (PMID: 16752378, 16773562, 21659347), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV001021527 SCV001183154 likely pathogenic Hereditary cancer-predisposing syndrome 2019-02-26 criteria provided, single submitter clinical testing Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Rarity in general population databases (dbsnp, esp, 1000 genomes)

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.