NM_000162.5(GCK):c.1130G>T (p.Arg377Leu) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 23, 2023
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:: RCV003331042.1

Allele description [Variation Report for NM_000162.5(GCK):c.1130G>T (p.Arg377Leu)]

NM_000162.5(GCK):c.1130G>T (p.Arg377Leu)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.1130G>T (p.Arg377Leu)

Other names:

NM_000162.5(GCK):c.1130G>T; p.Arg377Leu

HGVS:

NC_000007.14:g.44145620C>A
NG_008847.2:g.57551G>T
NM_000162.3:c.1130G>T
NM_000162.5:c.1130G>TMANE SELECT
NM_001354800.1:c.1130G>T
NM_001354801.1:c.119G>T
NM_001354802.1:c.-11G>T
NM_001354803.2:c.164G>T
NM_033507.3:c.1133G>T
NM_033508.3:c.1127G>T
NP_000153.1:p.Arg377Leu
NP_001341729.1:p.Arg377Leu
NP_001341730.1:p.Arg40Leu
NP_001341732.1:p.Arg55Leu
NP_277042.1:p.Arg378Leu
NP_277043.1:p.Arg376Leu
LRG_1074t1:c.1130G>T
LRG_1074t2:c.1133G>T
LRG_1074:g.57551G>T
LRG_1074p1:p.Arg377Leu
LRG_1074p2:p.Arg378Leu
NC_000007.13:g.44185219C>A

Protein change:

R376L

Links:

dbSNP: rs193922264

NCBI 1000 Genomes Browser:

rs193922264

Molecular consequence:

NM_001354802.1:c.-11G>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000162.5:c.1130G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.1130G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354801.1:c.119G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354803.2:c.164G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.1133G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.1127G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004038846	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Aug 23, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19790256, 32375122, 30245511, 21348868 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004038846

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Aug 23, 2023)

germline

clinical testing

PubMed (4)
[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

Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia.

Osbak KK, Colclough K, Saint-Martin C, Beer NL, Bellanné-Chantelot C, Ellard S, Gloyn AL.

Hum Mutat. 2009 Nov;30(11):1512-26. doi: 10.1002/humu.21110. Review.

PubMed [citation]

PMID:: 19790256

MODY2 in Asia: analysis of GCK mutations and clinical characteristics.

Zhou Y, Wang S, Wu J, Dong J, Liao L.

Endocr Connect. 2020 May;9(5):471-478. doi: 10.1530/EC-20-0074.

PubMed [citation]

PMID:: 32375122
PMCID:: PMC7274558

See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004038846.1

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

Description

Variant summary: GCK c.1130G>T (p.Arg377Leu) results in a non-conservative amino acid change located in the Hexokinase, C-terminal domain (IPR022673) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 234572 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1130G>T has been reported in the literature in individuals affected with features of Monogenic Diabetes (example, Osbak_2009, Borowiec_2012, Ma_2019, Zhou_2020, unpublished observations from the Clingen MODY expert panel). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 21348868, 30245511, 19790256, 32375122). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as pathogenic without evidence for independent evaluation. Based on the evidence outlined above, the variant was classified as VUS-possibly 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: Aug 4, 2024

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