U.S. flag

An official website of the United States government

NM_000162.5(GCK):c.679G>A (p.Gly227Ser) AND not provided

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 9, 2022
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:
RCV003060103.4

Allele description [Variation Report for NM_000162.5(GCK):c.679G>A (p.Gly227Ser)]

NM_000162.5(GCK):c.679G>A (p.Gly227Ser)

Gene:
GCK:glucokinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p13
Genomic location:
Preferred name:
NM_000162.5(GCK):c.679G>A (p.Gly227Ser)
HGVS:
  • NC_000007.14:g.44149760C>T
  • NG_008847.2:g.53411G>A
  • NM_000162.5:c.679G>AMANE SELECT
  • NM_001354800.1:c.679G>A
  • NM_033507.3:c.682G>A
  • NM_033508.3:c.676G>A
  • NP_000153.1:p.Gly227Ser
  • NP_001341729.1:p.Gly227Ser
  • NP_277042.1:p.Gly228Ser
  • NP_277043.1:p.Gly226Ser
  • LRG_1074t1:c.679G>A
  • LRG_1074t2:c.682G>A
  • LRG_1074:g.53411G>A
  • LRG_1074p1:p.Gly227Ser
  • LRG_1074p2:p.Gly228Ser
  • NC_000007.13:g.44189359C>T
Protein change:
G226S
Molecular consequence:
  • NM_000162.5:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354800.1:c.679G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033507.3:c.682G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033508.3:c.676G>A - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
effect on RNA splicing function [Variation Ontology: 0397]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV003439900Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Jun 9, 2022)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Mutations in GCK and HNF-1alpha explain the majority of cases with clinical diagnosis of MODY in Spain.

Estalella I, Rica I, Perez de Nanclares G, Bilbao JR, Vazquez JA, San Pedro JI, Busturia MA, Castaño L; Spanish MODY Group..

Clin Endocrinol (Oxf). 2007 Oct;67(4):538-46. Epub 2007 Jun 15.

PubMed [citation]
PMID:
17573900

Analysis of the GCK gene in 79 MODY type 2 patients: A multicenter Turkish study, mutation profile and description of twenty novel mutations.

Aykut A, Karaca E, Onay H, Gökşen D, Çetinkalp Ş, Eren E, Ersoy B, Çakır EP, Büyükinan M, Kara C, Anık A, Kırel B, Özen S, Atik T, Darcan Ş, Özkınay F.

Gene. 2018 Jan 30;641:186-189. doi: 10.1016/j.gene.2017.10.057. Epub 2017 Oct 19.

PubMed [citation]
PMID:
29056535
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003439900.2

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

Description

This missense change has been observed in individual(s) with clinical features of maturity-onset diabetes of the young (PMID: 17573900, 29056535; Invitae). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 227 of the GCK protein (p.Gly227Ser). This variant also falls at the last nucleotide of exon 6, which is part of the consensus splice site for this exon.

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

Last Updated: Sep 29, 2024