ClinVar Miner

Submissions for variant NM_000314.8(PTEN):c.389G>T (rs121909229)

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Total submissions: 17
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482735 SCV000566321 pathogenic not provided 2015-04-21 criteria provided, single submitter clinical testing The R130L missense variant in the PTEN gene has been reported previously inassociation with Cowden syndrome (Marsh et al., 1998). Introduction of the R130Lvariant into PTEN inactive cells failed to downregulate AKT phosphorylation (Spinelli etal., 2015). Additionally, another missense variant at the same residue (R130Q) iscommon variant in PTEN and has been reported several times in association with Cowdensyndrome (Kurose et al. 1999; Lobo et al., 2009). Therefore, we interpret R130L as a pathogenic variant.
Ambry Genetics RCV000490825 SCV000580044 pathogenic Hereditary cancer-predisposing syndrome 2017-09-18 criteria provided, single submitter clinical testing The p.R130L pathogenic mutation (also known as c.389G>T), located in coding exon 5 of the PTEN gene, results from a G to T substitution at nucleotide position 389. The arginine at codon 130 is replaced by leucine, an amino acid with dissimilar properties. This is a well-described mutation that has been reported in multiple individuals with classic Cowden syndrome or meeting at least relaxed International Cowden Consortium operational criteria for Cowden syndrome (Marsh DJ et al. Hum. Mol. Genet. 1998 Mar; 7(3):507-15; <span style="background-color:initial">Pilarski R et al. J. Med. Genet. 2011 Aug; 48(8):505-12; Ngeow J et al. J. Clin. Oncol. 2014 Jun; 32(17):1818-24; Bubien V et al. J. Med. Genet., 2013 Apr;50:255-63<span style="background-color:initial">). Furthermore, multiple additional pathogenic alterations at this position (including p.R130Q and p.R130P) have been reported in individuals with Cowden syndrome (Stenson et al. The Human Gene Mutation Database (HGMD&reg;): 2003 Update. Hum Mutat. 2003;21:577-581). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
GeneKor MSA RCV000490825 SCV000821769 likely pathogenic Hereditary cancer-predisposing syndrome 2020-01-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 130 of the PTEN protein. The arginine residue is highly conserved and there is a large physicochemical difference between arginine and leucine. This variant has been described in the international literature in an individual affected with Cowden syndrome (PMID: 9467011) and in an individual undergoing panel testing for hereditary syndrome (PMID: 31159747) The mutation database ClinVar contains entries for this variant (Variation ID:376509).
Clinical Genetics Karolinska University Hospital,Karolinska University Hospital RCV000482735 SCV001449541 pathogenic not provided 2019-09-19 criteria provided, single submitter clinical testing
Database of Curated Mutations (DoCM) RCV000419474 SCV000507198 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429740 SCV000507199 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440004 SCV000507200 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000422329 SCV000507201 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429105 SCV000507202 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439348 SCV000507203 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421727 SCV000507204 likely pathogenic Renal cell carcinoma, papillary, 1 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000431964 SCV000507205 likely pathogenic Neoplasm of uterine cervix 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443776 SCV000507206 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424192 SCV000507207 likely pathogenic Small cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434449 SCV000507208 likely pathogenic Adenocarcinoma of prostate 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443701 SCV000507209 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427024 SCV000507210 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only

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