NM_000162.5(GCK):c.566T>C (p.Ile189Thr) AND Maturity onset diabetes mellitus in young

Germline classification:: Likely pathogenic/Likely risk allele (2 submissions)
Last evaluated:: Mar 26, 2021
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:: RCV002350106.3

Allele description [Variation Report for NM_000162.5(GCK):c.566T>C (p.Ile189Thr)]

NM_000162.5(GCK):c.566T>C (p.Ile189Thr)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.566T>C (p.Ile189Thr)

Other names:

NM_000162.5(GCK):c.566T>C; p.Ile189Thr

HGVS:

NC_000007.14:g.44149982A>G
NG_008847.2:g.53189T>C
NM_000162.5:c.566T>CMANE SELECT
NM_001354800.1:c.566T>C
NM_033507.3:c.569T>C
NM_033508.3:c.563T>C
NP_000153.1:p.Ile189Thr
NP_001341729.1:p.Ile189Thr
NP_277042.1:p.Ile190Thr
NP_277043.1:p.Ile188Thr
LRG_1074t1:c.566T>C
LRG_1074t2:c.569T>C
LRG_1074:g.53189T>C
LRG_1074p1:p.Ile189Thr
LRG_1074p2:p.Ile190Thr
NC_000007.13:g.44189581A>G
NM_000162.3:c.566T>C

Protein change:

I188T

Links:

dbSNP: rs1554335441

NCBI 1000 Genomes Browser:

rs1554335441

Molecular consequence:

NM_000162.5:c.566T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.566T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.569T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.563T>C - 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

Recent activity

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Predicted glycosyl transferase [Arachnia propionica]
Predicted glycosyl transferase [Arachnia propionica]
gi|1540109295|emb|VEH68928.1|

Protein
Cyclomaltodextrinase [Arachnia propionica]
Cyclomaltodextrinase [Arachnia propionica]
gi|1540109890|emb|VEH69523.1|

Protein
Alphavirus Infections
Alphavirus Infections
Virus diseases caused by members of the ALPHAVIRUS genus of the family TOGAVIRIDAE.<br/>Year introduced: 1994

MeSH
Viral Vaccines
Viral Vaccines
Suspensions of attenuated or killed viruses administered for the prevention or treatment of infectious viral disease.<br/>Year introduced: 1965

MeSH
GBA3 glucosylceramidase beta 3 [Macaca mulatta]
GBA3 glucosylceramidase beta 3 [Macaca mulatta]
Gene ID:715716

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002605205	Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	criteria provided, single submitter (K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1)	Likely risk allele	unknown	research	PubMed (6) [See all records that cite these PMIDs] 33129248, 27269892, 32375122, 31197960, 30257192, 29510678 Citation Link,
SCV002647799	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Mar 26, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19790256, 22101819 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002605205

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

criteria provided, single submitter

(K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1)

Likely risk allele

unknown

research

PubMed (6)
[See all records that cite these PMIDs]

Citation Link,

SCV002647799

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Mar 26, 2021)

germline

clinical testing

PubMed (2)
[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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Clinical implications of the glucokinase impaired function - GCK MODY today.

Hulín J, Škopková M, Valkovičová T, Mikulajová S, Rosoľanková M, Papcun P, Gašperíková D, Staník J.

Physiol Res. 2020 Dec 22;69(6):995-1011. Epub 2020 Nov 2. Review.

PubMed [citation]

PMID:: 33129248
PMCID:: PMC8549873

GCK mutations in Chinese MODY2 patients: a family pedigree report and review of Chinese literature.

Ping Xiao Y, Hua Xu X, Lan Fang Y, Jiang L, Chen C, Liang L, Lin Wang C.

J Pediatr Endocrinol Metab. 2016 Aug 1;29(8):959-64. doi: 10.1515/jpem-2015-0354. Review.

PubMed [citation]

PMID:: 27269892

See all PubMed Citations (8)

Details of each submission

From Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic, SCV002605205.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		not provided	not provided	not provided	research	PubMed (6)

Description

Potent mutations in GCK gene is associated with poor secretion of insulin. Its associated with milder forms of diabetes, which can be controlled by diet . However, there is no sufficient evidence to ascertain the significance of rs1554335441 in MODY, yet.

#	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

From Ambry Genetics, SCV002647799.2

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

Description

The p.I189T variant (also known as c.566T>C), located in coding exon 5 of the GCK gene, results from a T to C substitution at nucleotide position 566. The isoleucine at codon 189 is replaced by threonine, an amino acid with similar properties. This variant has been detected in multiple unrelated individuals with maturity-onset diabetes of the young (Osbak KK et al. Hum Mutat, 2009 Nov;30:1512-26; Ambry internal data). Based on internal structural analysis, this alteration results in local structural destabilization (Petit P et al. Acta Crystallogr D Biol Crystallogr, 2011 Nov;67:929-35). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. 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: Jul 23, 2024

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