ClinVar Miner

Submissions for variant NM_000314.7(PTEN):c.389G>C (p.Arg130Pro) (rs121909229)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 16
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PTEN Variant Curation Expert Panel RCV000532163 SCV001244243 pathogenic PTEN hamartoma tumor syndrome 2019-11-22 reviewed by expert panel curation PTEN c.389G>C (p.Arg130Pro) meets criteria to be classified as 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). PS3: Phosphatase activity <50% of wild type (PMID 29706350) 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. PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (internal laboratory contributor SCV000185699.6)
Ambry Genetics RCV000130803 SCV000185699 likely pathogenic Hereditary cancer-predisposing syndrome 2018-03-29 criteria provided, single submitter clinical testing The p.R130P variant (also known as c.389G>C), located in coding exon 5 of the PTEN gene, results from a G to C substitution at nucleotide position 389. The arginine at codon 130 is replaced by proline, an amino acid with dissimilar properties. To date, there is no available literature regarding this proline variant, however there are several other missense variants affecting the same amino acid at codon 130 that have been classified as pathogenic and reported in multiple families with Cowden syndrome (Heindle M et al. Gastroenterology. 2012 May;142(5):1093-1096.e6; Marsh DJ et al. Hum Mol Genet. 1998 Mar;7(3):507-15). In addition, this arginine at codon 130 is a catalytic residue within the PTEN phosphatase signature motif, a known functional domain (Rodr&iacute;guez-Escudero I et al. Hum Mol Genet. 2011 Nov 1;20(21):4132-42). 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 majority of available evidence to date, this variant is likely to be pathogenic.
Invitae RCV000532163 SCV000645578 uncertain significance PTEN hamartoma tumor syndrome 2017-07-19 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 130 of the PTEN protein (p.Arg130Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PTEN-related disease. It has been observed in an individual with PTEN-associated phenotypes (Invitae). ClinVar contains an entry for this variant (Variation ID: 142018). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. A different missense substitution at this codon (p.Arg130Gln) has been determined to be pathogenic (PMID: 9915974, 23470840, 21822720, 23399955, 22327138, 22595938). This suggests that the arginine residue is critical for PTEN protein function and that other missense substitutions at this position may also be pathogenic. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Database of Curated Mutations (DoCM) RCV000437255 SCV000507211 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000443617 SCV000507212 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000426378 SCV000507213 likely pathogenic Squamous cell carcinoma of the head and neck 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000436686 SCV000507214 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418980 SCV000507215 likely pathogenic Adenocarcinoma of prostate 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000429247 SCV000507216 likely pathogenic Neoplasm of uterine cervix 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435997 SCV000507217 likely pathogenic Renal cell carcinoma, papillary, 1 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000418382 SCV000507218 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000428635 SCV000507219 likely pathogenic Breast neoplasm 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438856 SCV000507220 likely pathogenic Glioblastoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000421218 SCV000507221 likely pathogenic Uterine Carcinosarcoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427982 SCV000507222 likely pathogenic Small cell lung carcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000441753 SCV000507223 likely pathogenic Squamous cell lung carcinoma 2016-05-31 no assertion criteria provided literature only

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.