NM_000455.5(STK11):c.463G>T (p.Gly155Trp) AND Hereditary cancer-predisposing syndrome

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Mar 8, 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:: RCV000775651.10

Allele description [Variation Report for NM_000455.5(STK11):c.463G>T (p.Gly155Trp)]

NM_000455.5(STK11):c.463G>T (p.Gly155Trp)

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.463G>T (p.Gly155Trp)

Other names:

p.Gly155Trp

HGVS:

NC_000019.10:g.1219412G>T
NG_007460.2:g.35006G>T
NM_000455.5:c.463G>TMANE SELECT
NP_000446.1:p.Gly155Trp
NP_000446.1:p.Gly155Trp
LRG_319t1:c.463G>T
LRG_319:g.35006G>T
LRG_319p1:p.Gly155Trp
NC_000019.9:g.1219411G>T
NM_000455.4:c.463G>T

Protein change:

G155W

Links:

dbSNP: rs763353991

NCBI 1000 Genomes Browser:

rs763353991

Molecular consequence:

NM_000455.5:c.463G>T - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

Unknown function

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

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
SCV000910038	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 27, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29470806, 25741868
SCV001184609	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 8, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV002531699	Sema4, Sema4	criteria provided, single submitter (Sema4 Curation Guidelines)	Uncertain significance (Jun 2, 2021)	germline	curation	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

SCV000910038

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 27, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV001184609

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 8, 2024)

germline

clinical testing

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

Citation Link,

SCV002531699

Sema4, Sema4

criteria provided, single submitter

(Sema4 Curation Guidelines)

Uncertain significance
(Jun 2, 2021)

germline

curation

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, curation

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

Screening of over 1000 Indian patients with breast and/or ovarian cancer with a multi-gene panel: prevalence of BRCA1/2 and non-BRCA mutations.

Singh J, Thota N, Singh S, Padhi S, Mohan P, Deshwal S, Sur S, Ghosh M, Agarwal A, Sarin R, Ahmed R, Almel S, Chakraborti B, Raina V, DadiReddy PK, Smruti BK, Rajappa S, Dodagoudar C, Aggarwal S, Singhal M, Joshi A, Kumar R, et al.

Breast Cancer Res Treat. 2018 Jul;170(1):189-196. doi: 10.1007/s10549-018-4726-x. Epub 2018 Feb 22.

PubMed [citation]

PMID:: 29470806

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV000910038.4

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

Description

This missense variant replaces glycine with tryptophan at codon 155 of the STK11 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been in two individual from a cohort affected with breast and/or ovarian cancer (PMID: 29470806). This variant has been identified in 3/196374 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, SCV001184609.4

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

Description

The p.G155W variant (also known as c.463G>T), located in coding exon 3 of the STK11 gene, results from a G to T substitution at nucleotide position 463. The glycine at codon 155 is replaced by tryptophan, an amino acid with highly dissimilar properties. This variant was observed in a study of 1010 unrelated Indian patients with breast and/or ovarian cancer (Singh J et al. Breast Cancer Res Treat, 2018 Jul;170:189-196). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, 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

From Sema4, Sema4, SCV002531699.1

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

#	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

ClinVar

Relating variation to medicine