NM_000162.5(GCK):c.391T>C (p.Ser131Pro) AND Maturity-onset diabetes of the young type 2

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Aug 2, 2022
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:: RCV000017518.33

Allele description [Variation Report for NM_000162.5(GCK):c.391T>C (p.Ser131Pro)]

NM_000162.5(GCK):c.391T>C (p.Ser131Pro)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.391T>C (p.Ser131Pro)

HGVS:

NC_000007.14:g.44151048A>G
NG_008847.2:g.52123T>C
NM_000162.5:c.391T>CMANE SELECT
NM_001354800.1:c.391T>C
NM_033507.3:c.394T>C
NM_033508.3:c.388T>C
NP_000153.1:p.Ser131Pro
NP_001341729.1:p.Ser131Pro
NP_277042.1:p.Ser132Pro
NP_277043.1:p.Ser130Pro
LRG_1074t1:c.391T>C
LRG_1074t2:c.394T>C
LRG_1074:g.52123T>C
LRG_1074p1:p.Ser131Pro
LRG_1074p2:p.Ser132Pro
NC_000007.13:g.44190647A>G
NM_000162.3:c.391T>C
P35557:p.Ser131Pro

Protein change:

S130P; SER131PRO

Links:

UniProtKB: P35557#VAR_003697; OMIM: 138079.0007; dbSNP: rs104894010

NCBI 1000 Genomes Browser:

rs104894010

Molecular consequence:

NM_000162.5:c.391T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.391T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.394T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.388T>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

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tetraspanin-16 isoform 1 [Homo sapiens]
tetraspanin-16 isoform 1 [Homo sapiens]
gi|6912726|ref|NP_036598.1|

Protein
D001997 (1)
MeSH
Bronchopulmonary Dysplasia
Bronchopulmonary Dysplasia
A chronic lung disease developed after OXYGEN INHALATION THERAPY or mechanical ventilation (VENTILATION, MECHANICAL) usually occurring in certain premature infants (INFANT, PR...<br/>Year introduced: 1982

MeSH
B3GALT6 [Canis lupus dingo]
B3GALT6 [Canis lupus dingo]
Gene ID:112647021

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000037790	OMIM	no assertion criteria provided	Pathogenic (Jun 1, 1993)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002562171	Geisinger Clinic, Geisinger Health System	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Aug 2, 2022)	germline	research	PubMed (2) [See all records that cite these PMIDs] 25741868, 36257325
SCV003835349	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jul 1, 2022)	unknown	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

SCV000037790

OMIM

no assertion criteria provided

Pathogenic
(Jun 1, 1993)

germline

literature only

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

SCV002562171

Geisinger Clinic, Geisinger Health System

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Aug 2, 2022)

germline

research

PubMed (2)
[See all records that cite these PMIDs]

SCV003835349

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jul 1, 2022)

unknown

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	1	not provided	not provided	not provided	not provided	research
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification of glucokinase mutations in subjects with gestational diabetes mellitus.

Stoffel M, Bell KL, Blackburn CL, Powell KL, Seo TS, Takeda J, Vionnet N, Xiang KS, Gidh-Jain M, Pilkis SJ, et al.

Diabetes. 1993 Jun;42(6):937-40.

PubMed [citation]

PMID:: 8495817

Reduced penetrance of MODY-associated HNF1A/HNF4A variants but not GCK variants in clinically unselected cohorts.

Mirshahi UL, Colclough K, Wright CF, Wood AR, Beaumont RN, Tyrrell J, Laver TW, Stahl R, Golden A, Goehringer JM; Geisinger-Regeneron DiscovEHR Collaboration., Frayling TF, Hattersley AT, Carey DJ, Weedon MN, Patel KA.

Am J Hum Genet. 2022 Nov 3;109(11):2018-2028. doi: 10.1016/j.ajhg.2022.09.014. Epub 2022 Oct 17.

PubMed [citation]

PMID:: 36257325
PMCID:: PMC9674944

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000037790.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

Stoffel et al. (1993) found heterozygosity for a ser131-to-pro mutation in the GCK gene in an obese 31-year-old Puerto Rican woman with gestational diabetes (MODY2; 125851) in her first pregnancy. She reportedly had borderline elevated blood glucose levels at age 26. Stoffel et al. (1993) showed defective enzymatic properties of the enzyme carrying the ser131-to-pro mutation.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Geisinger Clinic, Geisinger Health System, SCV002562171.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	research	PubMed (2)

Description

PM2, PP1_Strong, PP4, PP2, PS3_Supporting

#	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

From Baylor Genetics, SCV003835349.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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