NM_000162.5(GCK):c.572G>A (p.Arg191Gln) AND Maturity onset diabetes mellitus in young

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 31, 2022
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:: RCV002347992.3

Allele description [Variation Report for NM_000162.5(GCK):c.572G>A (p.Arg191Gln)]

NM_000162.5(GCK):c.572G>A (p.Arg191Gln)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.572G>A (p.Arg191Gln)

Other names:

NM_000162.5(GCK):c.572G>A; p.Arg191Gln

HGVS:

NC_000007.14:g.44149976C>T
NG_008847.2:g.53195G>A
NM_000162.5:c.572G>AMANE SELECT
NM_001354800.1:c.572G>A
NM_033507.3:c.575G>A
NM_033508.3:c.569G>A
NP_000153.1:p.Arg191Gln
NP_001341729.1:p.Arg191Gln
NP_277042.1:p.Arg192Gln
NP_277043.1:p.Arg190Gln
LRG_1074t1:c.572G>A
LRG_1074t2:c.575G>A
LRG_1074:g.53195G>A
LRG_1074p1:p.Arg191Gln
LRG_1074p2:p.Arg192Gln
NC_000007.13:g.44189575C>T
NM_000162.3:c.572G>A

Protein change:

R190Q

Links:

dbSNP: rs886042610

NCBI 1000 Genomes Browser:

rs886042610

Molecular consequence:

NM_000162.5:c.572G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.572G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.575G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.569G>A - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002650655	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Oct 31, 2022)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 11508276, 16444761, 19309449, 20337973, 23295292, 27256596, 29056535, 29510678, 29927023, 34373539 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002650655

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Oct 31, 2022)

germline

clinical testing

PubMed (10)
[See all records that cite these PMIDs]

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

High prevalence of glucokinase mutations in Italian children with MODY. Influence on glucose tolerance, first-phase insulin response, insulin sensitivity and BMI.

Massa O, Meschi F, Cuesta-Munoz A, Caumo A, Cerutti F, Toni S, Cherubini V, Guazzarotti L, Sulli N, Matschinsky FM, Lorini R, Iafusco D, Barbetti F; Diabetes Study Group of the Italian Society of Paediatic Endocrinology and Diabetes (SIEDP)..

Diabetologia. 2001 Jul;44(7):898-905.

PubMed [citation]

PMID:: 11508276

Glucokinase mutations in young children with hyperglycemia.

Codner E, Deng L, Pérez-Bravo F, Román R, Lanzano P, Cassorla F, Chung WK.

Diabetes Metab Res Rev. 2006 Sep-Oct;22(5):348-55.

PubMed [citation]

PMID:: 16444761

See all PubMed Citations (10)

Details of each submission

From Ambry Genetics, SCV002650655.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

The p.R191Q pathogenic mutation (also known as c.572G>A), located in coding exon 5 of the GCK gene, results from a G to A substitution at nucleotide position 572. The arginine at codon 191 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been described in the heterozygous state in several unrelated individuals with maturity-onset diabetes of the young (MODY), type 2 (Caetano LA et al. Arq Bras Endocrinol Metabol, 2012 Nov;56:519-24; Pruhova S et al. Pediatr Diabetes, 2010 Dec;11:529-35; Codner E et al. Pediatr Diabetes, 2009 Sep;10:382-8; Codner E et al. Diabetes Metab Res Rev;22:348-55; Fulcoli FG et al. Nat Commun, 2016 06;7:11688; Aykut A et al. Gene, 2018 Jan;641:186-189; Yorifuji T et al. Pediatr Diabetes, 2018 11;19:1164-1172; Massa O et al. Diabetologia, 2001 Jul;44:898-905; Li X et al. BMC Pediatr, 2018 03;18:101; Al-Kandari H et al. Sci Rep, 2021 08;11:16060). This missense alteration is located in a region that has a low rate of benign missense variation (Lek M et al. Nature. 2016 Aug 18;536(7616):285-91; DECIPHER: Database of Chromosomal Imbalance and Phenotype in Humans using Ensembl Resources. Firth H.V. et al. 2009. Am.J.Hum.Genet. 84, 524-533 (DOI: dx.doi.org/10/1016/j.ajhg.2009.03.010)). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the supporting evidence, this variant is expected to be causative of maturity-onset diabetes of the young (MODY), type 2 and permanent neonatal diabetes; however, its clinical significance for GCK-related neonatal hyperinsulinemic hypoglycemia is 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: Sep 29, 2024

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