ClinVar Genomic variation as it relates to human health
NM_001126049.2(KLLN):c.-898G>A
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_001126049.2(KLLN):c.-898G>A
Variation ID: 127660 Accession: VCV000127660.45
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q23.31 10: 87863385 (GRCh38) [ NCBI UCSC ] 10: 89623142 (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 Aug 6, 2014 Apr 15, 2024 Nov 28, 2018 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000314.8:c.-1085C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NM_001126049.2:c.-898G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
5 prime UTR NC_000010.11:g.87863385C>T NC_000010.10:g.89623142C>T NG_007466.2:g.4948C>T NG_033079.1:g.5053G>A LRG_1087:g.5053G>A LRG_1087t1:c.-898G>A LRG_311:g.4948C>T LRG_311t1:c.-1084C>T - Protein change
- Other names
- NM_000314.6(PTEN):c.-1084C>T
- Canonical SPDI
- NC_000010.11:87863384:C: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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0.00559 (T)
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Allele frequency
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00262
Trans-Omics for Precision Medicine (TOPMed) 0.00295
1000 Genomes Project 30x 0.00500
1000 Genomes Project 0.00559
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
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
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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 |
3036 | 3528 | |
KLLN | - | - |
GRCh38 GRCh38 GRCh37 |
19 | 353 | |
LOC130004273 | - | - | - |
GRCh38 GRCh38 |
- | 286 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
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
Help
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
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
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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Uncertain significance (1) |
criteria provided, single submitter
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Dec 18, 2013 | RCV000115555.6 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Sep 23, 2020 | RCV000201312.23 | |
Likely benign (3) |
reviewed by expert panel
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Nov 28, 2018 | RCV000229583.10 | |
Benign (3) |
criteria provided, multiple submitters, no conflicts
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Mar 1, 2024 | RCV000586614.21 | |
Likely benign (1) |
criteria provided, single submitter
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Aug 14, 2017 | RCV000662713.4 | |
Likely benign (1) |
criteria provided, single submitter
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Jul 29, 2021 | RCV002498494.3 | |
Benign (1) |
criteria provided, single submitter
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Jan 6, 2023 | RCV003654199.1 |
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
Help
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
Help
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
Help
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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Likely benign
(Nov 28, 2018)
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reviewed by expert panel
Method: curation
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PTEN hamartoma tumor syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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Clingen PTEN Variant Curation Expert Panel, Clingen
Accession: SCV000886872.1
First in ClinVar: Jul 01, 2016 Last updated: Jul 01, 2016 |
Comment:
PTEN c.-1084C>T (NC_000010.10:g.89623142C>T) meets criteria to be classified as likely benign for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria … (more)
PTEN c.-1084C>T (NC_000010.10:g.89623142C>T) meets criteria to be classified as likely benign 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). BS1: Allele frequency of 0.0025 (0.25%, 38/14,966 alleles) in the European subpopulation of the gnomAD cohort. (PMID 27535533) BP2: At least three observations in cis and/or phase unknown with different pathogenic/likely pathogenic PTEN variants. (internal laboratory contributor(s) SCV000149464.4) BS2_P: Meets criteria for BS2 (observed in the homozygous state in at least one healthy or PHTS-unaffected individual) but BS1 is also applied. (PMID 27884173, internal laboratory contributor(s) SCV000149464.4, SCV000185343.1) (less)
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Uncertain significance
(Dec 18, 2013)
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criteria provided, single submitter
Method: clinical testing
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Neoplastic Syndromes, Hereditary
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000185343.1
First in ClinVar: Aug 06, 2014 Last updated: Aug 06, 2014 |
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Uncertain significance
(Mar 28, 2016)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000540135.1
First in ClinVar: Oct 31, 2015 Last updated: Oct 31, 2015 |
Comment:
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more)
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Region not covered by ExAC,reported in 1 proband, analysis of patient samples suggests possible impact to PTEN expression, but insufficient evidence for pathogenicity. (less)
Method: Genome/Exome Filtration
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Likely benign
(Aug 14, 2017)
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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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Counsyl
Accession: SCV000785463.2
First in ClinVar: Jul 15, 2018 Last updated: Jul 15, 2018 |
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Benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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None
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001138115.1
First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020 |
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Benign
(Jan 04, 2017)
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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: SCV000149464.6
First in ClinVar: May 21, 2014 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 25669429, 21417916, 17427195, 16773562, 12844284, 27884173, 27271787, 30528446, 33509259)
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Benign
(Aug 17, 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: SCV000284570.5
First in ClinVar: Jul 01, 2016 Last updated: Feb 20, 2024 |
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Benign
(Feb 09, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000696525.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
Comment:
Variant summary: The PTEN variant c.-1084C>T (also known as c.-1085C>T) involves the alteration of a non-conserved nucleotide in the 5'UTR region. One in silico tool … (more)
Variant summary: The PTEN variant c.-1084C>T (also known as c.-1085C>T) involves the alteration of a non-conserved nucleotide in the 5'UTR region. One in silico tool predicts a benign outcome for this variant. This variant was found in 28/5008 control chromosomes, predominantly observed in South Asians at a frequency of 0.0163599 (16/978). This frequency greatly exceeds the estimated maximal expected allele frequency of a pathogenic PTEN variant (0.0000063), suggesting this is likely a benign polymorphism found primarily in the populations of origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign/benign. Taken together, this variant is classified as benign. (less)
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Benign
(Apr 24, 2018)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000860984.1
First in ClinVar: Oct 31, 2015 Last updated: Oct 31, 2015 |
Number of individuals with the variant: 1
Sex: mixed
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Likely benign
(Sep 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV002071844.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
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Likely benign
(Jul 29, 2021)
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criteria provided, single submitter
Method: clinical testing
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Cowden syndrome 1
Malignant tumor of prostate Macrocephaly-autism syndrome Familial meningioma Glioma susceptibility 2
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002805067.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Benign
(Jan 06, 2023)
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criteria provided, single submitter
Method: clinical testing
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Cowden syndrome 4
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000604971.2
First in ClinVar: Oct 31, 2015 Last updated: Feb 20, 2024 |
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Benign
(Mar 01, 2024)
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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: SCV000780347.23
First in ClinVar: Mar 17, 2018 Last updated: Apr 15, 2024 |
Comment:
KLLN: BS1, BS2; PTEN: BS1, BS2
Number of individuals with the variant: 61
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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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Outcomes of retesting BRCA negative patients using multigene panels. | Yadav S | Familial cancer | 2017 | PMID: 27878467 |
Revisiting the morbid genome of Mendelian disorders. | Abouelhoda M | Genome biology | 2016 | PMID: 27884173 |
Analysis of protein-coding genetic variation in 60,706 humans. | Lek M | Nature | 2016 | PMID: 27535533 |
Frequency of germline PTEN mutations in differentiated thyroid cancer. | Nagy R | Thyroid : official journal of the American Thyroid Association | 2011 | PMID: 21417916 |
Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly. | Buxbaum JD | American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics | 2007 | PMID: 17427195 |
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 |
Germline PTEN promoter mutations and deletions in Cowden/Bannayan-Riley-Ruvalcaba syndrome result in aberrant PTEN protein and dysregulation of the phosphoinositol-3-kinase/Akt pathway. | Zhou XP | American journal of human genetics | 2003 | PMID: 12844284 |
Survival in asymptomatic primary biliary cirrhosis. Not as good as previously reported? | Kaplan MM | Gastroenterology | 1990 | PMID: 2338203 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PTEN | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/e2f7ef05-08bd-4ef3-ace7-9e1121c35952 | - | - | - | - |
Text-mined citations for rs538728843 ...
HelpRecord last updated Apr 15, 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.