NM_000162.5(GCK):c.491T>C (p.Leu164Pro) AND Maturity-onset diabetes of the young type 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 24, 2021
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:: RCV001293474.2

Allele description [Variation Report for NM_000162.5(GCK):c.491T>C (p.Leu164Pro)]

NM_000162.5(GCK):c.491T>C (p.Leu164Pro)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.491T>C (p.Leu164Pro)

HGVS:

NC_000007.14:g.44150057A>G
NG_008847.2:g.53114T>C
NM_000162.5:c.491T>CMANE SELECT
NM_001354800.1:c.491T>C
NM_033507.3:c.494T>C
NM_033508.3:c.488T>C
NP_000153.1:p.Leu164Pro
NP_001341729.1:p.Leu164Pro
NP_277042.1:p.Leu165Pro
NP_277043.1:p.Leu163Pro
LRG_1074t1:c.491T>C
LRG_1074t2:c.494T>C
LRG_1074:g.53114T>C
LRG_1074p1:p.Leu164Pro
LRG_1074p2:p.Leu165Pro
NC_000007.13:g.44189656A>G
NM_000162.3:c.491T>C

Protein change:

L163P

Links:

dbSNP: rs2096278847

NCBI 1000 Genomes Browser:

rs2096278847

Molecular consequence:

NM_000162.5:c.491T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.491T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.494T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.488T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Maturity-onset diabetes of the young type 2
Synonyms:: MODY type 2; Diabetes mellitus MODY type 2; MODY glucokinase-related; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007453; MedGen: C0342277; Orphanet: 552; OMIM: 125851

Recent activity

Clear Turn Off Turn On

Alg6 [Perognathus longimembris pacificus]
Alg6 [Perognathus longimembris pacificus]
Gene ID:125355246

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001482047	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Feb 24, 2021)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 11106831, 14517946, 18248649, 24578721, 25015100, 26552609 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001482047

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Feb 24, 2021)

germline

clinical testing

PubMed (6)
[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

Identification of glucokinase mutation in subjects with post-renal transplantation diabetes mellitus.

Nam JH, Lee HC, Kim YH, Cha BS, Song YD, Lim SK, Kim KR, Huh KB.

Diabetes Res Clin Pract. 2000 Dec;50(3):169-76.

PubMed [citation]

PMID:: 11106831

Glucokinase (GCK) mutations in hyper- and hypoglycemia: maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemia of infancy.

Gloyn AL.

Hum Mutat. 2003 Nov;22(5):353-62. Review.

PubMed [citation]

PMID:: 14517946

See all PubMed Citations (6)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001482047.1

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

Description

Variant summary: GCK c.491T>C (p.Leu164Pro) results in a non-conservative amino acid change located in the Hexokinase, N-terminal domain (IPR022672) 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 250018 control chromosomes. c.491T>C has been reported in the literature in multiple individuals affected with Maturity Onset Diabetes Of The Young 2/Neonatal Diabetes Mellitus (e.g. Nam_2000, Garin_2008, Raimondo_2014, Szopa_2015). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, indicating that the variant results in reduced GCK enzyme activity and lower affinity for glucose and ATP (e.g. Raimondo_2014). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as 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: Sep 29, 2024

ClinVar

Relating variation to medicine