ClinVar Genomic variation as it relates to human health
NM_000455.5(STK11):c.200T>C (p.Leu67Pro)
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_000455.5(STK11):c.200T>C (p.Leu67Pro)
Variation ID: 7445 Accession: VCV000007445.18
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 19p13.3 19: 1207113 (GRCh38) [ NCBI UCSC ] 19: 1207112 (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 22, 2016 Feb 14, 2024 Mar 3, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000455.5:c.200T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000446.1:p.Leu67Pro missense NC_000019.10:g.1207113T>C NC_000019.9:g.1207112T>C NG_007460.2:g.22707T>C LRG_319:g.22707T>C LRG_319t1:c.200T>C LRG_319p1:p.Leu67Pro Q15831:p.Leu67Pro - Protein change
- L67P
- Other names
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- Canonical SPDI
- NC_000019.10:1207112:T:C
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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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STK11 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2289 | 2567 |
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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Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
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Jul 15, 2021 | RCV000007871.18 | |
Pathogenic/Likely pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Mar 3, 2023 | RCV000440305.4 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Jul 1, 2016 | RCV000492681.2 |
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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Likely pathogenic
(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: SCV002057355.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
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Likely pathogenic
(May 25, 2016)
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criteria provided, single submitter
Method: clinical testing
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Peutz-Jeghers syndrome
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000488678.2
First in ClinVar: Aug 22, 2016 Last updated: Dec 24, 2022 |
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Likely pathogenic
(Aug 20, 2019)
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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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Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV001134840.3
First in ClinVar: Jan 05, 2020 Last updated: Jan 01, 2022 |
Comment:
Not found in the total gnomAD dataset, and the data is high quality (0/272834 chr). Found in at least one symptomatic patient. Predicted to have … (more)
Not found in the total gnomAD dataset, and the data is high quality (0/272834 chr). Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. Assessment of experimental evidence suggests this variant results in abnormal protein function. (less)
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Likely pathogenic
(Jul 01, 2016)
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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: SCV000580921.5
First in ClinVar: Jul 01, 2017 Last updated: Nov 29, 2022 |
Comment:
The p.L67P variant (also known as c.200T>C), located in coding exon 1 of the STK11 gene, results from a T to C substitution at nucleotide … (more)
The p.L67P variant (also known as c.200T>C), located in coding exon 1 of the STK11 gene, results from a T to C substitution at nucleotide position 200. The leucine at codon 67 is replaced by proline, an amino acid with similar properties. This alteration was seen in multiple unrelated individuals meeting diagnostic criteria for Peutz-Jeghers syndrome (Hemminki A et al. Nature 1998 Jan;391(6663):184-7; Hearle N et al. Clin. Cancer Res. 2006 May;12(10):3209-15; Ambry internal data). This variant was previously reported in the SNPDatabase as rs137853077. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 125000 alleles tested) in our clinical cohort. 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
(Mar 03, 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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GeneDx
Accession: SCV000514792.4
First in ClinVar: Mar 08, 2017 Last updated: Mar 18, 2023 |
Comment:
Published functional studies demonstrate a damaging effect: disrupted autophosphorylation of STK11 and absent kinase activity (Mehenni et al., 1998; Nezu et al., 1999; Ylikorkala et … (more)
Published functional studies demonstrate a damaging effect: disrupted autophosphorylation of STK11 and absent kinase activity (Mehenni et al., 1998; Nezu et al., 1999; Ylikorkala et al., 1999); 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: 16707622, 9428765, 11389158, 15121768, 29447078, 15863673, 15987703, 9887330, 10441497, 9837816) (less)
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Likely pathogenic
(Jan 14, 2020)
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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: SCV001391505.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces leucine with proline at codon 67 of the STK11 protein (p.Leu67Pro). The leucine residue is highly conserved and there is a … (more)
This sequence change replaces leucine with proline at codon 67 of the STK11 protein (p.Leu67Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Leu67 amino acid residue in STK11. Other variant(s) that disrupt this residue have been observed in individuals with STK11-related conditions (PMID: 11389158), which suggests that this may be a clinically significant amino acid residue. This variant has been reported to affect STK11 protein function (PMID: 9837816, 10441497, 9887330, 15987703). This variant has been observed in individuals with clinical features of Peutz-Jeghers syndrome (PMID: 9428765, 15121768). ClinVar contains an entry for this variant (Variation ID: 7445). This variant is not present in population databases (ExAC no frequency). (less)
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Pathogenic
(Jan 08, 1998)
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no assertion criteria provided
Method: literature only
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PEUTZ-JEGHERS SYNDROME
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000028076.4
First in ClinVar: Apr 04, 2013 Last updated: Jan 06, 2018 |
Comment on evidence:
In 1 of their 12 families with Peutz-Jeghers syndrome (PJS; 175200), Hemminki et al. (1998) found a heterozygous T-to-C transition in the STK11 gene, resulting … (more)
In 1 of their 12 families with Peutz-Jeghers syndrome (PJS; 175200), Hemminki et al. (1998) found a heterozygous T-to-C transition in the STK11 gene, resulting in a leu67-to-pro (L67P) substitution. (less)
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Likely pathogenic
(May 13, 2016)
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no assertion criteria provided
Method: literature only
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Peutz-Jeghers syndrome
(Somatic mutation)
Affected status: yes
Allele origin:
somatic
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Database of Curated Mutations (DoCM)
Accession: SCV000510527.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
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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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Frequency and spectrum of cancers in the Peutz-Jeghers syndrome. | Hearle N | Clinical cancer research : an official journal of the American Association for Cancer Research | 2006 | PMID: 16707622 |
LKB1 interacts with and phosphorylates PTEN: a functional link between two proteins involved in cancer predisposing syndromes. | Mehenni H | Human molecular genetics | 2005 | PMID: 15987703 |
Genotype-phenotype correlations in Peutz-Jeghers syndrome. | Amos CI | Journal of medical genetics | 2004 | PMID: 15121768 |
Peutz-Jeghers families unlinked to STK11/LKB1 gene mutations are highly predisposed to primitive biliary adenocarcinoma. | Olschwang S | Journal of medical genetics | 2001 | PMID: 11389158 |
Loss of cytoplasmic retention ability of mutant LKB1 found in Peutz-Jeghers syndrome patients. | Nezu J | Biochemical and biophysical research communications | 1999 | PMID: 10441497 |
Mutations and impaired function of LKB1 in familial and non-familial Peutz-Jeghers syndrome and a sporadic testicular cancer. | Ylikorkala A | Human molecular genetics | 1999 | PMID: 9887330 |
Loss of LKB1 kinase activity in Peutz-Jeghers syndrome, and evidence for allelic and locus heterogeneity. | Mehenni H | American journal of human genetics | 1998 | PMID: 9837816 |
A serine/threonine kinase gene defective in Peutz-Jeghers syndrome. | Hemminki A | Nature | 1998 | PMID: 9428765 |
http://docm.genome.wustl.edu/variants/ENST00000326873:c.200T>C | - | - | - | - |
Text-mined citations for rs137853077 ...
HelpRecord last updated Feb 20, 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.