NM_000455.5(STK11):c.33G>A (p.Met11Ile) AND Peutz-Jeghers syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 2, 2021
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:: RCV003102364.2

Allele description [Variation Report for NM_000455.5(STK11):c.33G>A (p.Met11Ile)]

NM_000455.5(STK11):c.33G>A (p.Met11Ile)

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.33G>A (p.Met11Ile)

HGVS:

NC_000019.10:g.1206946G>A
NG_007460.2:g.22540G>A
NM_000455.5:c.33G>AMANE SELECT
NM_001407255.1:c.33G>A
NP_000446.1:p.Met11Ile
NP_000446.1:p.Met11Ile
NP_001394184.1:p.Met11Ile
LRG_319t1:c.33G>A
LRG_319:g.22540G>A
LRG_319p1:p.Met11Ile
NC_000019.9:g.1206945G>A
NM_000455.4:c.33G>A
NR_176325.1:n.1169G>A

Protein change:

M11I

Molecular consequence:

NM_000455.5:c.33G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001407255.1:c.33G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV003225303	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 2, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29338689, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003225303

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 2, 2021)

germline

clinical testing

PubMed (2)
[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

Variants of cancer susceptibility genes in Korean BRCA1/2 mutation-negative patients with high risk for hereditary breast cancer.

Park JS, Lee ST, Nam EJ, Han JW, Lee JY, Kim J, Kim TI, Park HS.

BMC Cancer. 2018 Jan 16;18(1):83. doi: 10.1186/s12885-017-3940-y.

PubMed [citation]

PMID:: 29338689
PMCID:: PMC5769462

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003225303.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt STK11 protein function. This missense change has been observed in individual(s) with personal and/or family history of breast cancer (PMID: 29338689). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 11 of the STK11 protein (p.Met11Ile).

#	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: May 1, 2024

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