ClinVar Genomic variation as it relates to human health
NM_000314.8(PTEN):c.395G>T (p.Gly132Val)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000314.8(PTEN):c.395G>T (p.Gly132Val)
Variation ID: 7852 Accession: VCV000007852.20
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q23.31 10: 87933154 (GRCh38) [ NCBI UCSC ] 10: 89692911 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 11, 2015 Mar 16, 2024 Nov 21, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000314.8:c.395G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000305.3:p.Gly132Val missense NM_000314.6:c.395G>T NM_001304717.5:c.914G>T NP_001291646.4:p.Gly305Val missense NM_001304718.2:c.-356G>T 5 prime UTR NC_000010.11:g.87933154G>T NC_000010.10:g.89692911G>T NG_007466.2:g.74716G>T LRG_311:g.74716G>T LRG_311t1:c.395G>T P60484:p.Gly132Val - Protein change
- G132V, G305V
- Other names
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- Canonical SPDI
- NC_000010.11:87933153:G:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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PTEN | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh38 GRCh37 |
3009 | 3502 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
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The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
criteria provided, single submitter
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Nov 21, 2023 | RCV000008302.12 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Jun 28, 2015 | RCV000221956.2 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Oct 1, 2023 | RCV000489810.7 | |
Likely pathogenic (2) |
criteria provided, single submitter
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Sep 27, 2023 | RCV000656691.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 17, 2022 | RCV003460438.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 20, 2023 | RCV003924814.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
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The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
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The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Oct 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000577525.6
First in ClinVar: May 22, 2017 Last updated: Mar 04, 2023 |
Comment:
Published functional studies demonstrate a damaging effect: significantly reduced lipid phosphatase activity (Mighell et al., 2018); Not observed at significant frequency in large population cohorts … (more)
Published functional studies demonstrate a damaging effect: significantly reduced lipid phosphatase activity (Mighell et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 10923032, 10096247, 16752378, 23161105, 9256433, 26800850, 27221918, 21659347, 16773562, 27059323, 30787465, 24475377, 19457929, 29706350, 35227301, 32157856) (less)
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Likely pathogenic
(Sep 27, 2023)
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criteria provided, single submitter
Method: clinical testing
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Cowden syndrome 1
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV004188753.1
First in ClinVar: Dec 24, 2023 Last updated: Dec 24, 2023 |
Comment:
This variant is considered likely pathogenic. This variant is expected to disrupt protein structure [Myriad internal data]. This variant has been reported in multiple individuals … (more)
This variant is considered likely pathogenic. This variant is expected to disrupt protein structure [Myriad internal data]. This variant has been reported in multiple individuals with clinical features of gene-specific disease [PMID: 16752378, 16773562, 21194675]. (less)
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Pathogenic
(Nov 17, 2022)
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criteria provided, single submitter
Method: clinical testing
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Glioma susceptibility 2
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004204849.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Oct 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004127044.3
First in ClinVar: Nov 20, 2023 Last updated: Mar 10, 2024 |
Comment:
PTEN: PM1, PM2, PM5, PS4:Moderate, PP2, PP3
Number of individuals with the variant: 2
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Pathogenic
(Nov 20, 2023)
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criteria provided, single submitter
Method: clinical testing
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PTEN-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004738692.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
The PTEN c.395G>T variant is predicted to result in the amino acid substitution p.Gly132Val. This variant was reported in multiple unrelated individuals with PTEN hamartoma … (more)
The PTEN c.395G>T variant is predicted to result in the amino acid substitution p.Gly132Val. This variant was reported in multiple unrelated individuals with PTEN hamartoma tumor syndrome, including at least one de novo case (Tekin et al. 2006. PubMed ID: 16752378; Sarquis et al. 2006. PubMed ID: 16773562; Pilarski et al. 2011. PubMed ID: 21659347; Table S1, Pena-Couso et al. 2022. PubMed ID: 35227301). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. This variant is interpreted as pathogenic. (less)
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Likely pathogenic
(Jun 28, 2015)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000276872.7
First in ClinVar: May 29, 2016 Last updated: Nov 29, 2022 |
Comment:
The p.G132V variant (also known as c.395G>T), located in coding exon 5 of the PTEN gene, results from a G to T substitution at nucleotide … (more)
The p.G132V variant (also known as c.395G>T), located in coding exon 5 of the PTEN gene, results from a G to T substitution at nucleotide position 395. The glycine at codon 132 is replaced by valine, an amino acid with dissimilar properties. This variant was previously reported in the SNPDatabase as rs121909241. This variant was not reported in population-based cohorts in the following databases: NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. This variant has been described and confirmed to be de novo in a 4-year-old Turkish boy with clinical features of Cowden syndrome (Tekin M et al. Am. J. Med. Genet. A 2006 Jul; 140(13):1472-5). Two other alterations, p.G132D and p.G132A, have been reported in the same codon, and the former has been well-described in individuals with Cowden syndrome (Heindl M et al. Gastroenterology 2012 May; 142(5):1093-1096.e6, Derrey S et al. Surg Neurol 2004 May; 61(5):447-54; discussion 454). 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. (less)
Number of individuals with the variant: 1
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Pathogenic
(Nov 21, 2023)
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criteria provided, single submitter
Method: clinical testing
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PTEN hamartoma tumor syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000766782.7
First in ClinVar: Oct 11, 2015 Last updated: Feb 28, 2024 |
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 132 of the PTEN protein (p.Gly132Val). … (more)
This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 132 of the PTEN protein (p.Gly132Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with pediatric PTEN hamartoma tumor syndrome, with unusual phenotypic manifestations and Cowden syndrome (PMID: 16752378, 16773562, 21659347; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 7852). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is expected to disrupt PTEN function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects PTEN function (PMID: 29706350). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Jul 01, 2006)
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no assertion criteria provided
Method: literature only
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COWDEN SYNDROME 1
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000028509.2
First in ClinVar: Apr 04, 2013 Last updated: Jun 30, 2018 |
Comment on evidence:
In a 4.5-year-old Turkish boy with verrucous epidermal nevus, macrocephaly, progressive lipomatosis, and intestinal polyposis, suggestive of Cowden syndrome (CWS1; 158350), Tekin et al. (2006) … (more)
In a 4.5-year-old Turkish boy with verrucous epidermal nevus, macrocephaly, progressive lipomatosis, and intestinal polyposis, suggestive of Cowden syndrome (CWS1; 158350), Tekin et al. (2006) identified heterozygosity for a germline 395G-T transversion in the PTEN gene, resulting in a gly132-to-val (G132V) substitution. The mutation was not found in either parent. Loss of heterozygosity for chromosome 10q23 markers in the PTEN region was shown in tissue from a lipoma. The authors noted that the clinical presentation of this patient was similar to that of a 16-month-old boy with congenital left-sided verrucoid epidermal nevus, multiple lipoblastomas, and vascular anomalies in whom Smith et al. (2002) identified a deletion in the PTEN gene (601728.0032), but that limb overgrowth and asymmetry were absent in their patient. (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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A Saturation Mutagenesis Approach to Understanding PTEN Lipid Phosphatase Activity and Genotype-Phenotype Relationships. | Mighell TL | American journal of human genetics | 2018 | PMID: 29706350 |
Autoimmunity, intestinal lymphoid hyperplasia, and defects in mucosal B-cell homeostasis in patients with PTEN hamartoma tumor syndrome. | Heindl M | Gastroenterology | 2012 | PMID: 22266152 |
Predicting PTEN mutations: an evaluation of Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome clinical features. | Pilarski R | Journal of medical genetics | 2011 | PMID: 21659347 |
A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands. | Tan MH | American journal of human genetics | 2011 | PMID: 21194675 |
Distinct expression profiles for PTEN transcript and its splice variants in Cowden syndrome and Bannayan-Riley-Ruvalcaba syndrome. | Sarquis MS | American journal of human genetics | 2006 | PMID: 16773562 |
A germline PTEN mutation with manifestations of prenatal onset and verrucous epidermal nevus. | Tekin M | American journal of medical genetics. Part A | 2006 | PMID: 16752378 |
Association between Cowden syndrome and Lhermitte-Duclos disease: report of two cases and review of the literature. | Derrey S | Surgical neurology | 2004 | PMID: 15120218 |
Germline mutation of the tumour suppressor PTEN in Proteus syndrome. | Smith JM | Journal of medical genetics | 2002 | PMID: 12471211 |
Text-mined citations for rs121909241 ...
HelpRecord last updated Mar 17, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.