NM_000162.5(GCK):c.1175G>C (p.Arg392Pro) AND not provided

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Oct 13, 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:
RCV003561294.1

Allele description [Variation Report for NM_000162.5(GCK):c.1175G>C (p.Arg392Pro)]

NM_000162.5(GCK):c.1175G>C (p.Arg392Pro)

Gene:
GCK:glucokinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p13
Genomic location:
Preferred name:
NM_000162.5(GCK):c.1175G>C (p.Arg392Pro)
Other names:
NM_001354803.2:c.209G>C
HGVS:
  • NC_000007.14:g.44145575C>G
  • NG_008847.2:g.57596G>C
  • NM_000162.5:c.1175G>CMANE SELECT
  • NM_001354800.1:c.1175G>C
  • NM_001354801.1:c.164G>C
  • NM_001354802.1:c.35G>C
  • NM_001354803.2:c.209G>C
  • NM_033507.3:c.1178G>C
  • NM_033508.3:c.1172G>C
  • NP_000153.1:p.Arg392Pro
  • NP_001341729.1:p.Arg392Pro
  • NP_001341730.1:p.Arg55Pro
  • NP_001341731.1:p.Arg12Pro
  • NP_001341732.1:p.Arg70Pro
  • NP_277042.1:p.Arg393Pro
  • NP_277043.1:p.Arg391Pro
  • LRG_1074t1:c.1175G>C
  • LRG_1074t2:c.1178G>C
  • LRG_1074:g.57596G>C
  • LRG_1074p1:p.Arg392Pro
  • LRG_1074p2:p.Arg393Pro
  • NC_000007.13:g.44185174C>G
  • NC_000007.13:g.44185174C>G
Protein change:
R12P
Molecular consequence:
  • NM_000162.5:c.1175G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354800.1:c.1175G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354801.1:c.164G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354802.1:c.35G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354803.2:c.209G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033507.3:c.1178G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033508.3:c.1172G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004295131Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Oct 13, 2023) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Prevalence of monogenic diabetes in the population-based Norwegian Childhood Diabetes Registry.

Irgens HU, Molnes J, Johansson BB, Ringdal M, Skrivarhaug T, Undlien DE, Søvik O, Joner G, Molven A, Njølstad PR.

Diabetologia. 2013 Jul;56(7):1512-9. doi: 10.1007/s00125-013-2916-y. Epub 2013 Apr 27.

PubMed [citation]
PMID:
23624530

Glucokinase gene mutations: structural and genotype-phenotype analyses in MODY children from South Italy.

Tinto N, Zagari A, Capuano M, De Simone A, Capobianco V, Daniele G, Giugliano M, Spadaro R, Franzese A, Sacchetti L.

PLoS One. 2008 Apr 2;3(4):e1870. doi: 10.1371/journal.pone.0001870.

PubMed [citation]
PMID:
18382660
PMCID:
PMC2270336
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV004295131.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 392 of the GCK protein (p.Arg392Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of autosomal dominant maturity onset diabetes of the young (PMID: 23624530, 24097065). ClinVar contains an entry for this variant (Variation ID: 2574162). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GCK protein function. This variant disrupts the p.Arg392 amino acid residue in GCK. Other variant(s) that disrupt this residue have been observed in individuals with GCK-related conditions (PMID: 18382660, 24097065, 34746319), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Feb 20, 2024