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NM_000162.5(GCK):c.1106G>C (p.Arg369Pro) AND GCK-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 17, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV003416862.4

Allele description [Variation Report for NM_000162.5(GCK):c.1106G>C (p.Arg369Pro)]

NM_000162.5(GCK):c.1106G>C (p.Arg369Pro)

Gene:
GCK:glucokinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p13
Genomic location:
Preferred name:
NM_000162.5(GCK):c.1106G>C (p.Arg369Pro)
HGVS:
  • NC_000007.14:g.44145644C>G
  • NG_008847.2:g.57527G>C
  • NM_000162.5:c.1106G>CMANE SELECT
  • NM_001354800.1:c.1106G>C
  • NM_001354801.1:c.95G>C
  • NM_001354802.1:c.-35G>C
  • NM_001354803.2:c.140G>C
  • NM_033507.3:c.1109G>C
  • NM_033508.3:c.1103G>C
  • NP_000153.1:p.Arg369Pro
  • NP_001341729.1:p.Arg369Pro
  • NP_001341730.1:p.Arg32Pro
  • NP_001341732.1:p.Arg47Pro
  • NP_277042.1:p.Arg370Pro
  • NP_277043.1:p.Arg368Pro
  • LRG_1074t1:c.1106G>C
  • LRG_1074t2:c.1109G>C
  • LRG_1074:g.57527G>C
  • LRG_1074p1:p.Arg369Pro
  • LRG_1074p2:p.Arg370Pro
  • NC_000007.13:g.44185243C>G
  • NM_000162.3:c.1106G>C
Protein change:
R32P
Molecular consequence:
  • NM_001354802.1:c.-35G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000162.5:c.1106G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354800.1:c.1106G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354801.1:c.95G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354803.2:c.140G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033507.3:c.1109G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033508.3:c.1103G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
GCK-related disorder
Synonyms:
GCK-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004108175PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Jun 17, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004108175.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The GCK c.1106G>C variant is predicted to result in the amino acid substitution p.Arg369Pro. This variant has been reported in 11 affected individuals from a three generation family with Maturity Onset Diabetes of the Young (MODY), and segregated with the disorder within this family (Barrio et al 2002. PubMed ID: 12050210). Functional studies showed that this variant inhibits the stimulatory effect of insulin on the glucose metabolic response and prevented hormone-regulated GCK activation and S-nitrosylation (Ding SY et al 2009. PubMed ID: 19934346). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. An alternative variant at the same amino acid (p.Arg369Cys) has been reported in an individual with fasting hyperglycaemia (Gloyn et al. 2009. PubMed ID: 19002431). This variant is interpreted as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 19, 2024