ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.389G>A (p.Arg130Gln) (rs121909229)

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Total submissions: 22
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PTEN Variant Curation Expert Panel RCV000178761 SCV000840465 pathogenic PTEN hamartoma tumor syndrome 2017-10-18 reviewed by expert panel curation PTEN c.389G>A (p.R130Q) meets criteria to be classified as pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (Mester et al. 2018; manuscript in preparation). Please see a summary of the rules and criteria codes in the 'PTEN ACMG Specifications Summary' document (assertion method column). PM6_VS: At least four assumed de novo observations in a patient with the disease and no family history. (PMID 22595938, PMID 22327138, internal laboratory contributor(s) SCV000222111.11) PS3: Phosphatase activity <50% of wild type (PMID 10866302) PS4: Probands with phenotype specificity score of 4-15.5 (PMID 26798346, PMID 17526801, PMID 23335809, PMID 22266152) PM1: Located at a residue within a catalytic motif as defined by the ClinGen PTEN Expert Panel. PM2: Absent in large sequenced populations (PMID 27535533). 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.
Ambry Genetics RCV000131067 SCV000185997 pathogenic Hereditary cancer-predisposing syndrome 2017-09-06 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Other strong data supporting pathogenic classification,in silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Other data supporting pathogenic classification,Deficient protein function in appropriate functional assay(s)
GeneDx RCV000212880 SCV000222111 pathogenic not provided 2018-08-03 criteria provided, single submitter clinical testing This pathogenic variant is denoted PTEN c.389G>A at the cDNA level, p.Arg130Gln (R130Q) at the protein level, and results in the change of an Arginine to a Glutamine (CGA>CAA). This variant has been observed in several individuals with clinical features consistent with PTEN Hamartoma Tumor syndrome, with at least two de novo occurrences and segregation with disease reported (Kurose 1999, Hendriks 2003, Tan 2007, Mester 2012, Heindl 2012, O'Rourke 2012, Bubien 2013, Langer 2015). In an in vitro functional assay, PTEN Arg130Gln resulted in complete loss of phosphatase activity (Han 2000, Andr?s-Pons 2007). PTEN Arg130Gln was not observed in large population cohorts (Lek 2016). This variant is located in the phosphatase core domain as well as an ATP binding motif (Lee 1999, Lobo 2009, Molinari 2014). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, we consider this variant to be pathogenic.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000212880 SCV000230912 pathogenic not provided 2014-09-15 criteria provided, single submitter clinical testing
Invitae RCV000178761 SCV000541608 pathogenic PTEN hamartoma tumor syndrome 2018-12-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 130 of the PTEN protein (p.Arg130Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in numerous individuals affected with PTEN hamartoma tumor syndrome (PMID: 9915974, 23470840, 21822720, 23399955, 22327138). In one case, this variant was confirmed as being de novo in an affected individual (PMID: 22595938). ClinVar contains an entry for this variant (Variation ID: 7829). Different missense substitutions at this codon (p.Arg130Gly, p.Arg130Leu) have been determined to be pathogenic (PMID: 19457929, 24778394, 9467011, 10866302, 21828076, 25527629), suggesting that the arginine residue is critical for PTEN protein function. This variant is located within the catalytic core motif of the PTEN protein (HCKAGKGR, residues 123–130) (PMID: 10866302, 11875759). Experimental studies have shown that this missense change disrupts the phosphatase activity of the PTEN protein (PMID: 10866302, 17942903). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000008275 SCV000028482 pathogenic Cowden syndrome 1 2002-04-01 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435236 SCV000504382 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420647 SCV000504383 likely pathogenic Adenocarcinoma of prostate 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427853 SCV000504384 pathogenic Ovarian Neoplasms 2014-10-02 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000437651 SCV000504385 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420485 SCV000504386 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429864 SCV000504387 likely pathogenic Uterine cervical neoplasms 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440076 SCV000504388 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000419778 SCV000504389 likely pathogenic Neoplasm 2015-07-14 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429175 SCV000504390 likely pathogenic Neoplasm of the breast 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439397 SCV000504391 likely pathogenic Small cell lung cancer 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422627 SCV000504392 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432862 SCV000504393 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438720 SCV000504394 likely pathogenic Renal cell carcinoma, papillary, 1 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421074 SCV000504395 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000432211 SCV000504396 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
German Consortium for Hereditary Breast and Ovarian Cancer Center Cologne,University Hospital Cologne RCV000427853 SCV000924146 likely pathogenic Ovarian Neoplasms 2018-12-01 no assertion criteria provided research

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