NM_000162.5(GCK):c.629T>C (p.Met210Thr) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Feb 29, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000992058.9

Allele description [Variation Report for NM_000162.5(GCK):c.629T>C (p.Met210Thr)]

NM_000162.5(GCK):c.629T>C (p.Met210Thr)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.629T>C (p.Met210Thr)

Other names:

NM_000162.5(GCK):c.629T>C; p.Met210Thr

HGVS:

NC_000007.14:g.44149810A>G
NG_008847.2:g.53361T>C
NM_000162.5:c.629T>CMANE SELECT
NM_001354800.1:c.629T>C
NM_033507.3:c.632T>C
NM_033508.3:c.626T>C
NP_000153.1:p.Met210Thr
NP_001341729.1:p.Met210Thr
NP_277042.1:p.Met211Thr
NP_277043.1:p.Met209Thr
LRG_1074t1:c.629T>C
LRG_1074t2:c.632T>C
LRG_1074:g.53361T>C
LRG_1074p1:p.Met210Thr
LRG_1074p2:p.Met211Thr
NC_000007.13:g.44189409A>G
NM_000162.3:c.629T>C

Protein change:

M209T

Links:

dbSNP: rs80356654

NCBI 1000 Genomes Browser:

rs80356654

Molecular consequence:

NM_000162.5:c.629T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.629T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.632T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.626T>C - 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
SCV001144027	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Uncertain significance (Sep 21, 2018)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 9049484, 10525657, 19790256, 22389783, 25555642, 25723349, 26467025
SCV002069117	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 9, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005201998	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Feb 29, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001144027

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Uncertain significance
(Sep 21, 2018)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

SCV002069117

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 9, 2018)

germline

clinical testing

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

SCV005201998

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Feb 29, 2024)

germline

clinical testing

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
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification of 14 new glucokinase mutations and description of the clinical profile of 42 MODY-2 families.

Velho G, Blanché H, Vaxillaire M, Bellanné-Chantelot C, Pardini VC, Timsit J, Passa P, Deschamps I, Robert JJ, Weber IT, Marotta D, Pilkis SJ, Lipkind GM, Bell GI, Froguel P.

Diabetologia. 1997 Feb;40(2):217-24.

PubMed [citation]

PMID:: 9049484

Mutants of glucokinase cause hypoglycaemia- and hyperglycaemia syndromes and their analysis illuminates fundamental quantitative concepts of glucose homeostasis.

Davis EA, Cuesta-Muñoz A, Raoul M, Buettger C, Sweet I, Moates M, Magnuson MA, Matschinsky FM.

Diabetologia. 1999 Oct;42(10):1175-86.

PubMed [citation]

PMID:: 10525657

See all PubMed Citations (8)

Details of each submission

From Athena Diagnostics, SCV001144027.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

#	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

From Genetic Services Laboratory, University of Chicago, SCV002069117.1

#	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

From GeneDx, SCV005201998.1

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

Description

Published functional studies demonstrate that this variant causes significantly reduced enzyme activity (PMID: 10525657); Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; This variant is associated with the following publications: (PMID: 10525657, 18399931, 27913849, 14517946, 25555642, 9049484)

#	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: Sep 29, 2024

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