NM_000162.5(GCK):c.641A>G (p.Tyr214Cys) AND Hyperinsulinism due to glucokinase deficiency

Clinical significance:Pathogenic (Last evaluated: Aug 1, 2004)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000162.5(GCK):c.641A>G (p.Tyr214Cys)]

NM_000162.5(GCK):c.641A>G (p.Tyr214Cys)

GCK:glucokinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000162.5(GCK):c.641A>G (p.Tyr214Cys)
  • NC_000007.14:g.44149798T>C
  • NG_008847.2:g.53373A>G
  • NM_000162.5:c.641A>GMANE SELECT
  • NM_001354800.1:c.641A>G
  • NM_033507.3:c.644A>G
  • NM_033508.3:c.638A>G
  • NP_000153.1:p.Tyr214Cys
  • NP_001341729.1:p.Tyr214Cys
  • NP_277042.1:p.Tyr215Cys
  • NP_277043.1:p.Tyr213Cys
  • LRG_1074t1:c.641A>G
  • LRG_1074t2:c.644A>G
  • LRG_1074:g.53373A>G
  • LRG_1074p1:p.Tyr214Cys
  • LRG_1074p2:p.Tyr215Cys
  • NC_000007.13:g.44189397T>C
Protein change:
Y213C; TYR214CYS
OMIM: 138079.0013; dbSNP: rs104894015
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000162.5:c.641A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354800.1:c.641A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033507.3:c.644A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033508.3:c.638A>G - missense variant - [Sequence Ontology: SO:0001583]


Hyperinsulinism due to glucokinase deficiency (HHF3)
Hyperinsulinemic hypoglycemia familial 3
MONDO: MONDO:0011236; MedGen: C1865290; OMIM: 602485

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000037798OMIMno assertion criteria providedPathogenic
(Aug 1, 2004)
germlineliterature only

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only



Severe persistent hyperinsulinemic hypoglycemia due to a de novo glucokinase mutation.

Cuesta-Muñoz AL, Huopio H, Otonkoski T, Gomez-Zumaquero JM, Näntö-Salonen K, Rahier J, López-Enriquez S, García-Gimeno MA, Sanz P, Soriguer FC, Laakso M.

Diabetes. 2004 Aug;53(8):2164-8.

PubMed [citation]

Details of each submission

From OMIM, SCV000037798.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)


In a Finnish woman with severe hyperinsulinemic hypoglycemia from birth (602485), who had severe mental retardation and was still having hypoglycemic seizures when she died at age 29, Cuesta-Munoz et al. (2004) identified heterozygosity for a de novo tyr214-to-cys (Y214C) substitution in exon 6 of the GCK gene. Although paternity was confirmed, the mutation was not found in her parents or her 2 healthy sisters. Kinetic analysis revealed that this mutation had the highest activity index (130-fold over wildtype) of all naturally occurring activating GCK mutations described. Cuesta-Munoz et al. (2004) noted that this phenotype was considerably more severe than that of previously reported patients (see 138079.0009 and 138079.0012).

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

Support Center