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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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004038846Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Aug 23, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 20, 2024