NM_000162.5(GCK):c.704T>C (p.Met235Thr) AND Maturity-onset diabetes of the young type 2

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Apr 4, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000029911.3

Allele description [Variation Report for NM_000162.5(GCK):c.704T>C (p.Met235Thr)]

NM_000162.5(GCK):c.704T>C (p.Met235Thr)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.704T>C (p.Met235Thr)

HGVS:

NC_000007.14:g.44147809A>G
NG_008847.2:g.55362T>C
NM_000162.5:c.704T>CMANE SELECT
NM_001354800.1:c.704T>C
NM_033507.3:c.707T>C
NM_033508.3:c.701T>C
NP_000153.1:p.Met235Thr
NP_001341729.1:p.Met235Thr
NP_277042.1:p.Met236Thr
NP_277043.1:p.Met234Thr
LRG_1074t1:c.704T>C
LRG_1074t2:c.707T>C
LRG_1074:g.55362T>C
LRG_1074p1:p.Met235Thr
LRG_1074p2:p.Met236Thr
NC_000007.13:g.44187408A>G
NM_000162.3:c.704T>C

Protein change:

M234T

Links:

dbSNP: rs193922323

NCBI 1000 Genomes Browser:

rs193922323

Molecular consequence:

NM_000162.5:c.704T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.704T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.707T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.701T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000052566	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	likely pathogenic (Aug 18, 2011)	germline	curation, clinical testing	PubMed (3) [See all records that cite these PMIDs] 19790256, 18399931, 14517946 Citation Link,
SCV004808512	Centre for Inherited Metabolic Diseases, Karolinska University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 4, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000052566

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

likely pathogenic
(Aug 18, 2011)

germline

curation, clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link,

SCV004808512

Centre for Inherited Metabolic Diseases, Karolinska University Hospital

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 4, 2024)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	7	not provided	not provided	2	not provided	clinical testing, curation
not provided	germline	unknown	1	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

Diagnostic screening of MODY2/GCK mutations in the Norwegian MODY Registry.

Sagen JV, Bjørkhaug L, Molnes J, Raeder H, Grevle L, Søvik O, Molven A, Njølstad PR.

Pediatr Diabetes. 2008 Oct;9(5):442-9. doi: 10.1111/j.1399-5448.2008.00399.x. Epub 2008 Apr 9.

PubMed [citation]

PMID:: 18399931

See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000052566.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	curation	PubMed (3)
2	not provided	1	not provided	not provided	curation	PubMed (3)
3	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

"Found in a proband from Norwegian MODY Registry; controls not tested.": PubMed [ID: 18399931]
"This reference refers to variant as previously reported and cites this abstract: Bellane-Chantelot C, Iafusco D, Blanche H, Puca MR, Clauin S, Morel V, Le Gall I, Thomas G, Prisco F (1998). "Screening for mutations in the glucokinase (MODY2/GCK) and hepatocyte nuclear factor 1-a (MODY3/HNF-1a) genes in south Italian families (Abstract)." Diabetologia 41 Suppl. 1: A 109, 423. In this abstract, authors state that the variant was found in at least 1 Italian MODY family; number affected with variant and segregation status not specified; controls not tested.": PubMed [ID: 14517946]

Description

Converted during submission to Likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
2	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
3	germline	unknown	not provided	Blood	assert pathogenicity		not provided	not provided	not provided	not provided

From Centre for Inherited Metabolic Diseases, Karolinska University Hospital, SCV004808512.1

#	Individuals	Chromosomes Tested	Family History	Method	Citations
1	1	not provided	not provided	clinical testing	PubMed (1)
2	1	not provided	not provided	clinical testing	PubMed (1)
3	1	not provided	not provided	clinical testing	PubMed (1)
4	1	not provided	not provided	clinical testing	PubMed (1)
5	1	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		1	not provided	not provided	not provided
2	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
3	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
4	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided
5	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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