VCV000527838.6 - ClinVar

NM_000455.5(STK11):c.795_796dup (p.Asn266fs)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic

2 out of 2 submissions contributed to this classification

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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000455.5(STK11):c.795_796dup (p.Asn266fs)

Variation ID: 527838 Accession: VCV000527838.6

Type and length

Microsatellite, 2 bp

Location

Cytogenetic: 19p13.3 19: 1221270-1221271 (GRCh38) [ NCBI UCSC ] 19: 1221269-1221270 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	May 28, 2018	Oct 5, 2025	Aug 8, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_000455.5:c.795_796dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000446.1:p.Asn266fs	frameshift
NC_000019.10:g.1221271GA[3]
NC_000019.9:g.1221270GA[3]
NG_007460.2:g.36865GA[3]
LRG_319:g.36865GA[3]

... more HGVS ... less HGVS

Protein change

N266fs

Other names

Canonical SPDI

NC_000019.10:1221270:GAGA:GAGAGA

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA658799089 dbSNP: rs1555738656 VarSome

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
Gene	OMIM	HI score Help 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.
STK11		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	2737	3043

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.
Peutz-Jeghers syndrome	Pathogenic (1)	criteria provided, single submitter	Dec 15, 2017	RCV000632838.6
Hereditary cancer-predisposing syndrome	Pathogenic (1)	criteria provided, single submitter	Aug 8, 2025	RCV005742082.1

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.	Expand all rows Collapse all rows 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.
Pathogenic (Dec 15, 2017) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Peutz-Jeghers syndrome	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000754034.5 First in ClinVar: May 28, 2018 Last updated: Feb 25, 2025	Publications: PubMed (2) PubMed: 15188174‚ 16287113 Comment: show This variant has not been reported in the literature in individuals with STK11-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asn266Argfs*22) in the STK11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in STK11 are known to be pathogenic (PMID: 15188174, 16287113). For these reasons, this variant has been classified as Pathogenic. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Pathogenic (Aug 08, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Hereditary cancer-predisposing syndrome	Ambry Genetics Accession: SCV006438765.1 First in ClinVar: Oct 05, 2025 Last updated: Oct 05, 2025	Comment: show The c.795_796dupGA pathogenic mutation, located in coding exon 6 of the STK11 gene, results from a duplication of GA at nucleotide position 795, causing a translational frameshift with a predicted alternate stop codon (p.N266Rfs*22). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

This variant has not been reported in the literature in individuals with STK11-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Asn266Argfs*22) in the STK11 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in STK11 are known to be pathogenic (PMID: 15188174, 16287113). For these reasons, this variant has been classified as Pathogenic.

Comment:

The c.795_796dupGA pathogenic mutation, located in coding exon 6 of the STK11 gene, results from a duplication of GA at nucleotide position 795, causing a translational frameshift with a predicted alternate stop codon (p.N266Rfs*22). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
High proportion of large genomic STK11 deletions in Peutz-Jeghers syndrome.	Aretz S	Human mutation	2005	PMID: 16287113
Relative frequency and morphology of cancers in STK11 mutation carriers.	Lim W	Gastroenterology	2004	PMID: 15188174

Text-mined citations for rs1555738656 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Dec 07, 2025