NM_000162.5(GCK):c.941T>C (p.Leu314Pro) AND Maturity onset diabetes mellitus in young

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Mar 22, 2019
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:: RCV002376921.4

Allele description [Variation Report for NM_000162.5(GCK):c.941T>C (p.Leu314Pro)]

NM_000162.5(GCK):c.941T>C (p.Leu314Pro)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.941T>C (p.Leu314Pro)

HGVS:

NC_000007.14:g.44146541A>G
NG_008847.2:g.56630T>C
NM_000162.5:c.941T>CMANE SELECT
NM_001354800.1:c.941T>C
NM_001354801.1:c.8+78T>C
NM_033507.3:c.944T>C
NM_033508.3:c.938T>C
NP_000153.1:p.Leu314Pro
NP_001341729.1:p.Leu314Pro
NP_277042.1:p.Leu315Pro
NP_277043.1:p.Leu313Pro
LRG_1074t1:c.941T>C
LRG_1074t2:c.944T>C
LRG_1074:g.56630T>C
LRG_1074p1:p.Leu314Pro
LRG_1074p2:p.Leu315Pro
NC_000007.13:g.44186140A>G
NM_000162.3:c.941T>C

Protein change:

L313P

Links:

dbSNP: rs1554334886

NCBI 1000 Genomes Browser:

rs1554334886

Molecular consequence:

NM_001354801.1:c.8+78T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000162.5:c.941T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.941T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.944T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.938T>C - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002605122	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 risk allele	unknown	research	PubMed (6) [See all records that cite these PMIDs] 33129248, 27269892, 32375122, 31197960, 30257192, 29510678 Citation Link,
SCV002685023	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Mar 22, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002605122

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 risk allele

unknown

research

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

Citation Link,

SCV002685023

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Mar 22, 2019)

germline

clinical testing

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

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 (7)

Details of each submission

From Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic, SCV002605122.1

#	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 rs1554334886 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, SCV002685023.2

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

Description

The p.L314P variant (also known as c.941T>C), located in coding exon 8 of the GCK gene, results from a T to C substitution at nucleotide position 941. The leucine at codon 314 is replaced by proline, an amino acid with similar properties. This variant was identified in one individual with a clinical diagnosis of maturity-onset diabetes of the young (Garin I et al. Clin. Endocrinol. (Oxf), 2008 Jun;68:873-8). 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 available evidence to date, 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

ClinVar

Relating variation to medicine