NM_000455.5(STK11):c.1244G>A (p.Arg415His) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Aug 15, 2023
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:: RCV002305502.3

Allele description [Variation Report for NM_000455.5(STK11):c.1244G>A (p.Arg415His)]

NM_000455.5(STK11):c.1244G>A (p.Arg415His)

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.1244G>A (p.Arg415His)

HGVS:

NC_000019.10:g.1226589G>A
NG_007460.2:g.42183G>A
NM_000455.5:c.1244G>AMANE SELECT
NP_000446.1:p.Arg415His
NP_000446.1:p.Arg415His
LRG_319t1:c.1244G>A
LRG_319:g.42183G>A
LRG_319p1:p.Arg415His
NC_000019.9:g.1226588G>A
NM_000455.4:c.1244G>A

Protein change:

R415H

Links:

dbSNP: rs775978755

NCBI 1000 Genomes Browser:

rs775978755

Molecular consequence:

NM_000455.5:c.1244G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002599675	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Nov 1, 2022)	germline	clinical testing	Citation Link,
SCV004221270	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Uncertain significance (Aug 15, 2023)	unknown	clinical testing	PubMed (4) [See all records that cite these PMIDs] 30287823, 33020649, 30885352, 26467025

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002599675

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Nov 1, 2022)

germline

clinical testing

Citation Link,

SCV004221270

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Uncertain significance
(Aug 15, 2023)

unknown

clinical testing

PubMed (4)
[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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Germline pathogenic variants of 11 breast cancer genes in 7,051 Japanese patients and 11,241 controls.

Momozawa Y, Iwasaki Y, Parsons MT, Kamatani Y, Takahashi A, Tamura C, Katagiri T, Yoshida T, Nakamura S, Sugano K, Miki Y, Hirata M, Matsuda K, Spurdle AB, Kubo M.

Nat Commun. 2018 Oct 4;9(1):4083. doi: 10.1038/s41467-018-06581-8.

PubMed [citation]

PMID:: 30287823
PMCID:: PMC6172276

Clinical utility of circulating tumor DNA sequencing in advanced gastrointestinal cancer: SCRUM-Japan GI-SCREEN and GOZILA studies.

Nakamura Y, Taniguchi H, Ikeda M, Bando H, Kato K, Morizane C, Esaki T, Komatsu Y, Kawamoto Y, Takahashi N, Ueno M, Kagawa Y, Nishina T, Kato T, Yamamoto Y, Furuse J, Denda T, Kawakami H, Oki E, Nakajima T, Nishida N, Yamaguchi K, et al.

Nat Med. 2020 Dec;26(12):1859-1864. doi: 10.1038/s41591-020-1063-5. Epub 2020 Oct 5.

PubMed [citation]

PMID:: 33020649

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV002599675.2

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

Description

Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28900777, 30287823)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV004221270.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

In the published literature, this variant has been reported in individuals with breast cancer (PMID: 30287823 (2018)) and colorectal cancer (PMID: 33020649 (2020)). This variant has also been reported as a somatic variant in an individual with lung cancer (PMID: 30885352 (2019)). The frequency of this variant in the general population, 0.00012 (1/171592 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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