NM_000455.5(STK11):c.454C>T (p.Gln152Ter) AND Peutz-Jeghers syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 11, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001951192.5

Allele description [Variation Report for NM_000455.5(STK11):c.454C>T (p.Gln152Ter)]

NM_000455.5(STK11):c.454C>T (p.Gln152Ter)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

19p13.3

Genomic location:

Preferred name:

NM_000455.5(STK11):c.454C>T (p.Gln152Ter)

HGVS:

NC_000019.10:g.1219403C>T
NG_007460.2:g.34997C>T
NM_000455.5:c.454C>TMANE SELECT
NP_000446.1:p.Gln152Ter
LRG_319:g.34997C>T
NC_000019.9:g.1219402C>T

Protein change:

Q152*

Links:

dbSNP: rs2145422504

NCBI 1000 Genomes Browser:

rs2145422504

Molecular consequence:

NM_000455.5:c.454C>T - nonsense - [Sequence Ontology: SO:0001587]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002241349	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 11, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 9887330, 12865922, 15188174, 16287113, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002241349

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 11, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Mutations and impaired function of LKB1 in familial and non-familial Peutz-Jeghers syndrome and a sporadic testicular cancer.

Ylikorkala A, Avizienyte E, Tomlinson IP, Tiainen M, Roth S, Loukola A, Hemminki A, Johansson M, Sistonen P, Markie D, Neale K, Phillips R, Zauber P, Twama T, Sampson J, Järvinen H, Mäkelä TP, Aaltonen LA.

Hum Mol Genet. 1999 Jan;8(1):45-51.

PubMed [citation]

PMID:: 9887330

Further observations on LKB1/STK11 status and cancer risk in Peutz-Jeghers syndrome.

Lim W, Hearle N, Shah B, Murday V, Hodgson SV, Lucassen A, Eccles D, Talbot I, Neale K, Lim AG, O'Donohue J, Donaldson A, Macdonald RC, Young ID, Robinson MH, Lee PW, Stoodley BJ, Tomlinson I, Alderson D, Holbrook AG, Vyas S, Swarbrick ET, et al.

Br J Cancer. 2003 Jul 21;89(2):308-13.

PubMed [citation]

PMID:: 12865922
PMCID:: PMC2394252

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV002241349.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1456529). This premature translational stop signal has been observed in individual(s) with clinical features of Peutz-Jeghers syndrome (PMID: 9887330, 12865922). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln152*) 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

Last Updated: Feb 20, 2024

ClinVar

Relating variation to medicine