NM_000455.5(STK11):c.790_793del (p.Phe264fs) 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:: RCV000632833.12

Allele description [Variation Report for NM_000455.5(STK11):c.790_793del (p.Phe264fs)]

NM_000455.5(STK11):c.790_793del (p.Phe264fs)

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.790_793del (p.Phe264fs)

HGVS:

NC_000019.10:g.1221268_1221271del
NG_007460.2:g.36862_36865del
NM_000455.5:c.790_793delMANE SELECT
NP_000446.1:p.Phe264fs
NP_000446.1:p.Phe264fs
LRG_319t1:c.790_793del
LRG_319:g.36862_36865del
LRG_319p1:p.Phe264fs
NC_000019.9:g.1221264_1221267del
NC_000019.9:g.1221267_1221270del
NM_000455.4:c.790_793del
NM_000455.4:c.790_793delTTTG
p.Phe264fs

Protein change:

F264fs

Links:

dbSNP: rs121913320

NCBI 1000 Genomes Browser:

rs121913320

Molecular consequence:

NM_000455.5:c.790_793del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000754029	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 6, 2023)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 9809980, 15863673, 17010210, 23718779, 26979979, 15188174, 16287113, 28492532
SCV002057379	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 15, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004931663	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

SCV000754029

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 6, 2023)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

SCV002057379

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 15, 2021)

germline

clinical testing

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

SCV004931663

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	no	not provided	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

STK11 mutations in Peutz-Jeghers syndrome and sporadic colon cancer.

Resta N, Simone C, Mareni C, Montera M, Gentile M, Susca F, Gristina R, Pozzi S, Bertario L, Bufo P, Carlomagno N, Ingrosso M, Rossini FP, Tenconi R, Guanti G.

Cancer Res. 1998 Nov 1;58(21):4799-801.

PubMed [citation]

PMID:: 9809980

STK11 genotyping and cancer risk in Peutz-Jeghers syndrome.

Schumacher V, Vogel T, Leube B, Driemel C, Goecke T, Möslein G, Royer-Pokora B.

J Med Genet. 2005 May;42(5):428-35. No abstract available.

PubMed [citation]

PMID:: 15863673
PMCID:: PMC1736065

See all PubMed Citations (9)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000754029.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 372523). This variant is also known as c.787del4. This premature translational stop signal has been observed in individual(s) with Peutz-Jeghers syndrome (PMID: 9809980, 15863673, 16287113, 17010210, 23718779, 26979979). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Phe264Argfs*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).

#	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 Genome-Nilou Lab, SCV002057379.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV004931663.1

#	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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