NM_000162.5(GCK):c.1087G>A (p.Asp363Asn) AND Maturity onset diabetes mellitus in young

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Mar 4, 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:: RCV002431386.4

Allele description [Variation Report for NM_000162.5(GCK):c.1087G>A (p.Asp363Asn)]

NM_000162.5(GCK):c.1087G>A (p.Asp363Asn)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.1087G>A (p.Asp363Asn)

Other names:

NM_000162.5(GCK):c.1087G>A; p.Asp363Asn

HGVS:

NC_000007.14:g.44145663C>T
NG_008847.2:g.57508G>A
NM_000162.5:c.1087G>AMANE SELECT
NM_001354800.1:c.1087G>A
NM_001354801.1:c.76G>A
NM_001354802.1:c.-54G>A
NM_001354803.2:c.121G>A
NM_033507.3:c.1090G>A
NM_033508.3:c.1084G>A
NP_000153.1:p.Asp363Asn
NP_001341729.1:p.Asp363Asn
NP_001341730.1:p.Asp26Asn
NP_001341732.1:p.Asp41Asn
NP_277042.1:p.Asp364Asn
NP_277043.1:p.Asp362Asn
LRG_1074t1:c.1087G>A
LRG_1074t2:c.1090G>A
LRG_1074:g.57508G>A
LRG_1074p1:p.Asp363Asn
LRG_1074p2:p.Asp364Asn
NC_000007.13:g.44185262C>T
NM_000162.3:c.1087G>A

Protein change:

D26N

Links:

dbSNP: rs1064793134

NCBI 1000 Genomes Browser:

rs1064793134

Molecular consequence:

NM_001354802.1:c.-54G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000162.5:c.1087G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.1087G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354801.1:c.76G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354803.2:c.121G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.1090G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.1084G>A - 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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NSMCE1 NSE1 homolog, SMC5-SMC6 complex component [Homo sapiens]
NSMCE1 NSE1 homolog, SMC5-SMC6 complex component [Homo sapiens]
Gene ID:197370

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002605096	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)	Likely pathogenic	unknown	research	PubMed (6) [See all records that cite these PMIDs] 33129248, 27269892, 32375122, 31197960, 30257192, 29510678 Citation Link,
SCV002730876	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 4, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19790256, 36257325 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002605096

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)

Likely pathogenic

unknown

research

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

Citation Link,

SCV002730876

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 4, 2024)

germline

clinical testing

PubMed (2)
[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
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 (8)

Details of each submission

From Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic, SCV002605096.1

#	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 rs1064793134 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, SCV002730876.2

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

Description

The p.D363N variant (also known as c.1087G>A), located in coding exon 9 of the GCK gene, results from a G to A substitution at nucleotide position 1087. The aspartic acid at codon 363 is replaced by asparagine, an amino acid with highly similar properties. This variant was reported in multiple individuals with features consistent with GCK-related maturity-onset diabetes of the young (Osbak KK et al. Hum Mutat, 2009 Nov;30:1512-26; Mirshahi UL et al. Am J Hum Genet, 2022 Nov;109:2018-2028; Tanaka S et al. Endocr J, 2023 Jun 28;70(6):629-634). In an assay testing GCK function, this variant showed a functionally abnormal result (Tanaka S et al. Endocr J, 2023 Jun 28;70(6):629-634). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, 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 7, 2024

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