NM_000162.5(GCK):c.540T>G (p.Asn180Lys) AND Maturity onset diabetes mellitus in young

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 23, 2016
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:: RCV002343405.2

Allele description [Variation Report for NM_000162.5(GCK):c.540T>G (p.Asn180Lys)]

NM_000162.5(GCK):c.540T>G (p.Asn180Lys)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.540T>G (p.Asn180Lys)

HGVS:

NC_000007.14:g.44150008A>C
NG_008847.2:g.53163T>G
NM_000162.5:c.540T>GMANE SELECT
NM_001354800.1:c.540T>G
NM_033507.3:c.543T>G
NM_033508.3:c.537T>G
NP_000153.1:p.Asn180Lys
NP_001341729.1:p.Asn180Lys
NP_277042.1:p.Asn181Lys
NP_277043.1:p.Asn179Lys
LRG_1074t1:c.540T>G
LRG_1074t2:c.543T>G
LRG_1074:g.53163T>G
LRG_1074p1:p.Asn180Lys
LRG_1074p2:p.Asn181Lys
NC_000007.13:g.44189607A>C
NM_000162.3:c.540T>G

Protein change:

N179K

Links:

dbSNP: rs1554335444

NCBI 1000 Genomes Browser:

rs1554335444

Molecular consequence:

NM_000162.5:c.540T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.540T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.543T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.537T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Maturity onset diabetes mellitus in young (MODY)
Synonyms:: Mason type diabetes
Identifiers:: MONDO: MONDO:0018911; MedGen: C0342276; Orphanet: 552; OMIM: 606391; Human Phenotype Ontology: HP:0004904

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LOC124421891 [Vespa crabro]
LOC124421891 [Vespa crabro]
Gene ID:124421891

Gene
Cystadenoma
Cystadenoma
A benign neoplasm derived from glandular epithelium, in which cystic accumulations of retained secretions are formed. In some instances, considerable portions of the neoplasm,...<br/>

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002650509	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Dec 23, 2016)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 10753050, 21978167 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002650509

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Dec 23, 2016)

germline

clinical testing

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

Citation Link

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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

A high prevalence of glucokinase mutations in gestational diabetic subjects selected by clinical criteria.

Ellard S, Beards F, Allen LI, Shepherd M, Ballantyne E, Harvey R, Hattersley AT.

Diabetologia. 2000 Feb;43(2):250-3.

PubMed [citation]

PMID:: 10753050

The glucokinase mutation p.T206P is common among MODY patients of Jewish Ashkenazi descent.

Gozlan Y, Tenenbaum A, Shalitin S, Lebenthal Y, Oron T, Cohen O, Phillip M, Gat-Yablonski G.

Pediatr Diabetes. 2012 Sep;13(6):e14-21. doi: 10.1111/j.1399-5448.2011.00822.x. Epub 2011 Oct 7.

PubMed [citation]

PMID:: 21978167

Details of each submission

From Ambry Genetics, SCV002650509.2

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

Description

The p.N180K variant (also known as c.540T>G), located in coding exon 5 of the GCK gene, results from a T to G substitution at nucleotide position 540. The asparagine at codon 180 is replaced by lysine, an amino acid with similar properties. In a small study (n = 15) of women with a history of gestational diabetes (GDM), persistent fasting hyperclycemia outside of pregnancy (diet controlled), and a first degree relative with either elevated fasting glucose or a history of type II or GDMs, one individual was identified to be heterozygous for this variant; two of her relatives with elevated fasting plasma glucose were also heterozygous (Ellard S et al. Diabetologia, 2000 Feb;43:250-3). In another study, a 3 year old female with a clinical diagnosis of MODY, and her mother with a history of GDM, each carried the p.N180K alteration (Gozlan Y et al. Pediatr Diabetes, 2012 Sep;13:e14-21). This variant was not reported in the ExAC database, with coverage at this position. 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 majority of available evidence to date, this variant is likely to be pathogenic.

#	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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