NM_000455.5(STK11):c.829G>T (p.Asp277Tyr) AND Peutz-Jeghers syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 13, 2024
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:: RCV001340811.7

Allele description [Variation Report for NM_000455.5(STK11):c.829G>T (p.Asp277Tyr)]

NM_000455.5(STK11):c.829G>T (p.Asp277Tyr)

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.829G>T (p.Asp277Tyr)

HGVS:

NC_000019.10:g.1221307G>T
NG_007460.2:g.36901G>T
NM_000455.5:c.829G>TMANE SELECT
NP_000446.1:p.Asp277Tyr
LRG_319t1:c.829G>T
LRG_319:g.36901G>T
NC_000019.9:g.1221306G>T
NM_000455.4:c.829G>T

Protein change:

D277Y

Links:

dbSNP: rs1555738692

NCBI 1000 Genomes Browser:

rs1555738692

Molecular consequence:

NM_000455.5:c.829G>T - 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
SCV001534639	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 13, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19892943, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001534639

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 13, 2024)

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

Structure of the LKB1-STRAD-MO25 complex reveals an allosteric mechanism of kinase activation.

Zeqiraj E, Filippi BM, Deak M, Alessi DR, van Aalten DM.

Science. 2009 Dec 18;326(5960):1707-11. doi: 10.1126/science.1178377. Epub 2009 Nov 5.

PubMed [citation]

PMID:: 19892943
PMCID:: PMC3518268

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001534639.4

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

Description

This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 277 of the STK11 protein (p.Asp277Tyr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with STK11-related conditions. ClinVar contains an entry for this variant (Variation ID: 1037627). 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 with a negative predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect STK11 function (PMID: 19892943). 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.

#	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: Oct 8, 2024

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