ClinVar Genomic variation as it relates to human health
NM_000455.5(STK11):c.71C>T (p.Thr24Met)
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.
Uncertain significance(5); Likely benign(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000455.5(STK11):c.71C>T (p.Thr24Met)
Variation ID: 403777 Accession: VCV000403777.21
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19p13.3 19: 1206984 (GRCh38) [ NCBI UCSC ] 19: 1206983 (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 Feb 19, 2018 May 1, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000455.5:c.71C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000446.1:p.Thr24Met missense NC_000019.10:g.1206984C>T NC_000019.9:g.1206983C>T NG_007460.2:g.22578C>T LRG_319:g.22578C>T LRG_319t1:c.71C>T LRG_319p1:p.Thr24Met - Protein change
- T24M
- Other names
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- Canonical SPDI
- NC_000019.10:1206983: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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Allele frequency
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The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00001
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Trans-Omics for Precision Medicine (TOPMed) 0.00001
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
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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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STK11 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2344 | 2616 |
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
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
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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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Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Jan 31, 2024 | RCV000472539.13 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Apr 7, 2023 | RCV000568581.14 | |
Uncertain significance (1) |
criteria provided, single submitter
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Aug 18, 2023 | RCV003477937.1 |
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
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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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Likely benign
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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Peutz-Jeghers syndrome
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000541139.8
First in ClinVar: Apr 17, 2017 Last updated: Feb 20, 2024 |
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Uncertain significance
(Aug 18, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
unknown
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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004221288.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
Comment:
In the published literature, this variant has been reported in individuals with prostate cancer (PMID: 29368341 (2018)) and acute myeloid leukemia (PMID: 26580448 (2015)). In … (more)
In the published literature, this variant has been reported in individuals with prostate cancer (PMID: 29368341 (2018)) and acute myeloid leukemia (PMID: 26580448 (2015)). In a breast cancer association study, this variant was reported both in healthy individuals and those with breast cancer (PMID: 33471991 (2021), see also LOVD (https://databases.lovd.nl/shared/variants/STK11)). The frequency of this variant in the general population, 0.0000082 (2/245242 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. (less)
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Uncertain Significance
(Jan 11, 2024)
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criteria provided, single submitter
Method: clinical testing
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Peutz-Jeghers syndrome
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
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All of Us Research Program, National Institutes of Health
Accession: SCV004816308.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
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Comment:
This missense variant replaces threonine with methionine at codon 24 of the STK11 protein. Computational prediction is inconclusive regarding the impact of this variant on … (more)
This missense variant replaces threonine with methionine at codon 24 of the STK11 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with leukemia (PMID: 26580448) and prostate cancer (PMID: 29368341) This variant has been identified in 2/245242 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
Number of individuals with the variant: 4
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Uncertain significance
(Jan 18, 2023)
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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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Color Diagnostics, LLC DBA Color Health
Accession: SCV000686676.5
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces threonine with methionine at codon 24 of the STK11 protein. Computational prediction suggests that this variant may not impact protein structure … (more)
This missense variant replaces threonine with methionine at codon 24 of the STK11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with leukemia (PMID: 26580448) and prostate cancer (PMID: 29368341). This variant has been identified in 2/245242 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
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Likely benign
(Apr 07, 2023)
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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: SCV000672318.6
First in ClinVar: Jan 01, 2018 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Uncertain significance
(Jul 15, 2021)
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criteria provided, single submitter
Method: clinical testing
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Peutz-Jeghers syndrome
Affected status: no
Allele origin:
germline
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Genome-Nilou Lab
Accession: SCV002057731.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
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Uncertain significance
(Sep 16, 2021)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Sema4, Sema4
Accession: SCV002531724.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022
Comment:
The STK11 c.71C>T (p.T24M) variant has been reported in heterozygosity in at least three individuals with breast cancer, prostate cancer, or acute megakaryoblastic leukemia (PMID: … (more)
The STK11 c.71C>T (p.T24M) variant has been reported in heterozygosity in at least three individuals with breast cancer, prostate cancer, or acute megakaryoblastic leukemia (PMID: 33471991, 29368341, 26580448). It was observed in 2/245242 chromosomes in the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654). The variant has been reported in ClinVar (Variation ID 403777). Functional studies have not been performed, and in silico predictions of the variant's effect on protein function are inconclusive. The evidence is insufficient to meet ACMG/AMP criteria for classifying the variant as benign or pathogenic. Thus, the clinical significance of this variant is currently uncertain. (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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Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
Intraductal/ductal histology and lymphovascular invasion are associated with germline DNA-repair gene mutations in prostate cancer. | Isaacsson Velho P | The Prostate | 2018 | PMID: 29368341 |
Germline Mutations in Predisposition Genes in Pediatric Cancer. | Zhang J | The New England journal of medicine | 2015 | PMID: 26580448 |
Text-mined citations for rs770503805 ...
HelpRecord last updated May 08, 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.