NM_000162.5(GCK):c.1174C>T (p.Arg392Cys) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Dec 22, 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:: RCV000711758.12

Allele description [Variation Report for NM_000162.5(GCK):c.1174C>T (p.Arg392Cys)]

NM_000162.5(GCK):c.1174C>T (p.Arg392Cys)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.1174C>T (p.Arg392Cys)

Other names:

NM_000162.5(GCK):c.1174C>T; p.Arg392Cys

HGVS:

NC_000007.14:g.44145576G>A
NG_008847.2:g.57595C>T
NM_000162.5:c.1174C>TMANE SELECT
NM_001354800.1:c.1174C>T
NM_001354801.1:c.163C>T
NM_001354802.1:c.34C>T
NM_001354803.2:c.208C>T
NM_033507.3:c.1177C>T
NM_033508.3:c.1171C>T
NP_000153.1:p.Arg392Cys
NP_001341729.1:p.Arg392Cys
NP_001341730.1:p.Arg55Cys
NP_001341731.1:p.Arg12Cys
NP_001341732.1:p.Arg70Cys
NP_277042.1:p.Arg393Cys
NP_277043.1:p.Arg391Cys
LRG_1074t1:c.1174C>T
LRG_1074t2:c.1177C>T
LRG_1074:g.57595C>T
LRG_1074p1:p.Arg392Cys
LRG_1074p2:p.Arg393Cys
NC_000007.13:g.44185175G>A
NM_000162.3:c.1174C>T
NM_000162.4:c.1174C>T

Protein change:

R12C

Links:

dbSNP: rs1167124132

NCBI 1000 Genomes Browser:

rs1167124132

Molecular consequence:

NM_000162.5:c.1174C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.1174C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354801.1:c.163C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354802.1:c.34C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354803.2:c.208C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.1171C>T - 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
SCV000842152	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Dec 22, 2023)	unknown	clinical testing	PubMed (8) [See all records that cite these PMIDs] 29758564, 34746319, 34789499, 36208030, 36257325, 37101203, 9662401, 26467025
SCV001816829	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (May 5, 2021)	germline	clinical testing	Citation Link,
SCV002070819	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 2, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000842152

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(Dec 22, 2023)

unknown

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

SCV001816829

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(May 5, 2021)

germline

clinical testing

Citation Link,

SCV002070819

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 2, 2019)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	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	clinical testing

Citations

PubMed

Monogenic diabetes in overweight and obese youth diagnosed with type 2 diabetes: the TODAY clinical trial.

Kleinberger JW, Copeland KC, Gandica RG, Haymond MW, Levitsky LL, Linder B, Shuldiner AR, Tollefsen S, White NH, Pollin TI.

Genet Med. 2018 Jun;20(6):583-590. doi: 10.1038/gim.2017.150. Epub 2017 Oct 12.

PubMed [citation]

PMID:: 29758564
PMCID:: PMC5955780

Identification of Novel GCK and HNF4α Gene Variants in Japanese Pediatric Patients with Onset of Diabetes before 17 Years of Age.

Katashima R, Matsumoto M, Watanabe Y, Moritani M, Yokota I.

J Diabetes Res. 2021;2021:7216339. doi: 10.1155/2021/7216339.

PubMed [citation]

PMID:: 34746319
PMCID:: PMC8570896

See all PubMed Citations (9)

Details of each submission

From Athena Diagnostics, SCV000842152.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This variant has been identified in multiple unrelated individuals with MODY. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Assessment of experimental evidence suggests this variant results in abnormal protein function. (PMID: 37101203)

#	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 GeneDx, SCV001816829.1

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

Description

In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 24430320, 18382660, 14517946, 18271687, 9662401, 14517956)

#	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 Genetic Services Laboratory, University of Chicago, SCV002070819.1

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

#	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

Last Updated: May 19, 2024

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