NM_000162.5(GCK):c.1310C>G (p.Thr437Ser) AND Maturity onset diabetes mellitus in young

Germline classification:: Uncertain significance/Uncertain risk allele (2 submissions)
Last evaluated:: Apr 4, 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:: RCV002385433.3

Allele description [Variation Report for NM_000162.5(GCK):c.1310C>G (p.Thr437Ser)]

NM_000162.5(GCK):c.1310C>G (p.Thr437Ser)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.1310C>G (p.Thr437Ser)

HGVS:

NC_000007.14:g.44145224G>C
NG_008847.2:g.57947C>G
NM_000162.5:c.1310C>GMANE SELECT
NM_001354800.1:c.1310C>G
NM_001354801.1:c.299C>G
NM_001354802.1:c.170C>G
NM_001354803.2:c.344C>G
NM_033507.3:c.1313C>G
NM_033508.3:c.1307C>G
NP_000153.1:p.Thr437Ser
NP_001341729.1:p.Thr437Ser
NP_001341730.1:p.Thr100Ser
NP_001341731.1:p.Thr57Ser
NP_001341732.1:p.Thr115Ser
NP_277042.1:p.Thr438Ser
NP_277043.1:p.Thr436Ser
LRG_1074t1:c.1310C>G
LRG_1074t2:c.1313C>G
LRG_1074:g.57947C>G
LRG_1074p1:p.Thr437Ser
LRG_1074p2:p.Thr438Ser
NC_000007.13:g.44184823G>C
NM_000162.3:c.1310C>G

Protein change:

T100S

Links:

dbSNP: rs1185622190

NCBI 1000 Genomes Browser:

rs1185622190

Molecular consequence:

NM_000162.5:c.1310C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.1310C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354801.1:c.299C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354802.1:c.170C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354803.2:c.344C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.1313C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.1307C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Maturity onset diabetes mellitus in young (MODY)
Synonyms:: Mason type diabetes
Identifiers:: MONDO: MONDO:0018911; MedGen: C0342276; Orphanet: 552; OMIM: 606391; Human Phenotype Ontology: HP:0004904

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002605057	Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	criteria provided, single submitter (K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1)	Uncertain risk allele	unknown	research	PubMed (6) [See all records that cite these PMIDs] 33129248, 27269892, 32375122, 31197960, 30257192, 29510678 Citation Link,
SCV002693817	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Apr 4, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002605057

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

criteria provided, single submitter

(K & H Uppaluri Personalized Medicine Clinic Variant Classification & Assertion Criteria_Updated V.1)

Uncertain risk allele

unknown

research

PubMed (6)
[See all records that cite these PMIDs]

Citation Link,

SCV002693817

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Apr 4, 2022)

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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Clinical implications of the glucokinase impaired function - GCK MODY today.

Hulín J, Škopková M, Valkovičová T, Mikulajová S, Rosoľanková M, Papcun P, Gašperíková D, Staník J.

Physiol Res. 2020 Dec 22;69(6):995-1011. Epub 2020 Nov 2. Review.

PubMed [citation]

PMID:: 33129248
PMCID:: PMC8549873

GCK mutations in Chinese MODY2 patients: a family pedigree report and review of Chinese literature.

Ping Xiao Y, Hua Xu X, Lan Fang Y, Jiang L, Chen C, Liang L, Lin Wang C.

J Pediatr Endocrinol Metab. 2016 Aug 1;29(8):959-64. doi: 10.1515/jpem-2015-0354. Review.

PubMed [citation]

PMID:: 27269892

See all PubMed Citations (6)

Details of each submission

From Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic, SCV002605057.1

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

Description

Potent mutations in GCK gene is associated with poor secretion of insulin. Its associated with milder forms of diabetes, which can be controlled by diet . However, there is no sufficient evidence to ascertain the significance of rs1185622190 in MODY, yet.

#	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

From Ambry Genetics, SCV002693817.2

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

Description

The p.T437S variant (also known as c.1310C>G), located in coding exon 10 of the GCK gene, results from a C to G substitution at nucleotide position 1310. The threonine at codon 437 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: May 1, 2024

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