NM_000455.5(STK11):c.56C>T (p.Ser19Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 12, 2022
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:: RCV000777388.7

Allele description [Variation Report for NM_000455.5(STK11):c.56C>T (p.Ser19Leu)]

NM_000455.5(STK11):c.56C>T (p.Ser19Leu)

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.56C>T (p.Ser19Leu)

HGVS:

NC_000019.10:g.1206969C>T
NG_007460.2:g.22563C>T
NM_000455.5:c.56C>TMANE SELECT
NP_000446.1:p.Ser19Leu
NP_000446.1:p.Ser19Leu
LRG_319t1:c.56C>T
LRG_319:g.22563C>T
LRG_319p1:p.Ser19Leu
NC_000019.9:g.1206968C>T
NM_000455.4:c.56C>T

Protein change:

S19L

Links:

dbSNP: rs1426026332

NCBI 1000 Genomes Browser:

rs1426026332

Molecular consequence:

NM_000455.5:c.56C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary cancer-predisposing syndrome
Synonyms:: Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000913250	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 12, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001186441	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Dec 2, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000913250

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 12, 2022)

germline

clinical testing

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

SCV001186441

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Dec 2, 2021)

germline

clinical testing

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

Citation Link

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

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

Germ-line variants identified by next generation sequencing in a panel of estrogen and cancer associated genes correlate with poor clinical outcome in Lynch syndrome patients.

Jóri B, Kamps R, Xanthoulea S, Delvoux B, Blok MJ, Van de Vijver KK, de Koning B, Oei FT, Tops CM, Speel EJ, Kruitwagen RF, Gomez-Garcia EB, Romano A.

Oncotarget. 2015 Dec 1;6(38):41108-22. doi: 10.18632/oncotarget.5694.

PubMed [citation]

PMID:: 26517685
PMCID:: PMC4747393

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000913250.3

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

Description

This missense variant replaces serine with leucine at codon 19 of the STK11 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with STK11-related disorders in the literature. This variant has been identified in 1/241614 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is 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

From Ambry Genetics, SCV001186441.4

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

Description

The p.S19L variant (also known as c.56C>T), located in coding exon 1 of the STK11 gene, results from a C to T substitution at nucleotide position 56. The serine at codon 19 is replaced by leucine, an amino acid with dissimilar properties. This alteration was detected in a cohort of 35 endometrial cancer patients who also had a mismatch repair (MMR) pathogenic mutation (Jóri B et al. Oncotarget, 2015 Dec;6:41108-22). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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 7, 2024

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