NM_000455.5(STK11):c.540del (p.Asn181fs) AND Peutz-Jeghers syndrome

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Feb 12, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV002289947.6

Allele description [Variation Report for NM_000455.5(STK11):c.540del (p.Asn181fs)]

NM_000455.5(STK11):c.540del (p.Asn181fs)

Gene:

STK11:serine/threonine kinase 11 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

19p13.3

Genomic location:

Preferred name:

NM_000455.5(STK11):c.540del (p.Asn181fs)

HGVS:

NC_000019.10:g.1220448del
NG_007460.2:g.36042del
NM_000455.5:c.540delMANE SELECT
NP_000446.1:p.Asn181fs
LRG_319t1:c.540del
LRG_319:g.36042del
NC_000019.9:g.1220444del
NC_000019.9:g.1220447del
NM_000455.4:c.540del
NM_000455.4:c.540delG
NM_000455.5:c.540del

Protein change:

N181fs

Links:

dbSNP: rs1131690939

NCBI 1000 Genomes Browser:

rs1131690939

Molecular consequence:

NM_000455.5:c.540del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Peutz-Jeghers syndrome (PJS)
Synonyms:: Polyposis, hamartomatous intestinal; Polyps-and-spots syndrome; Peutz-Jeghers polyposis; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008280; MeSH: D010580; MedGen: C0031269; Orphanet: 2869; OMIM: 175200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002579129	MGZ Medical Genetics Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 3, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003443798	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 5, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15188174, 16287113, 21118512, 28492532
SCV004933433	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Pathogenic (Feb 12, 2024)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002579129

MGZ Medical Genetics Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 3, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003443798

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 5, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV004933433

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Pathogenic
(Feb 12, 2024)

unknown

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Relative frequency and morphology of cancers in STK11 mutation carriers.

Lim W, Olschwang S, Keller JJ, Westerman AM, Menko FH, Boardman LA, Scott RJ, Trimbath J, Giardiello FM, Gruber SB, Gille JJ, Offerhaus GJ, de Rooij FW, Wilson JH, Spigelman AD, Phillips RK, Houlston RS.

Gastroenterology. 2004 Jun;126(7):1788-94.

PubMed [citation]

PMID:: 15188174

See all PubMed Citations (5)

Details of each submission

From MGZ Medical Genetics Center, SCV002579129.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003443798.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 545746). This sequence change creates a premature translational stop signal (p.Asn181Thrfs*106) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Peutz-Jeghers syndrome (PMID: 21118512).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV004933433.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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