NM_000162.5(GCK):c.365T>C (p.Leu122Pro) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 27, 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:: RCV003555343.2

Allele description [Variation Report for NM_000162.5(GCK):c.365T>C (p.Leu122Pro)]

NM_000162.5(GCK):c.365T>C (p.Leu122Pro)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.365T>C (p.Leu122Pro)

Other names:

NM_033508.3:c.362T>C

HGVS:

NC_000007.14:g.44151074A>G
NG_008847.2:g.52097T>C
NM_000162.5:c.365T>CMANE SELECT
NM_001354800.1:c.365T>C
NM_033507.3:c.368T>C
NM_033508.3:c.362T>C
NP_000153.1:p.Leu122Pro
NP_001341729.1:p.Leu122Pro
NP_277042.1:p.Leu123Pro
NP_277043.1:p.Leu121Pro
LRG_1074t1:c.365T>C
LRG_1074t2:c.368T>C
LRG_1074:g.52097T>C
LRG_1074p1:p.Leu122Pro
LRG_1074p2:p.Leu123Pro
NC_000007.13:g.44190673A>G

Protein change:

L121P

Molecular consequence:

NM_000162.5:c.365T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.365T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.368T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.362T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004295185	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 27, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 15928245, 11508276, 32468610, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004295185

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 27, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

Citations

PubMed

Half of clinically defined maturity-onset diabetes of the young patients in Denmark do not have mutations in HNF4A, GCK, and TCF1.

Johansen A, Ek J, Mortensen HB, Pedersen O, Hansen T.

J Clin Endocrinol Metab. 2005 Aug;90(8):4607-14. Epub 2005 May 31.

PubMed [citation]

PMID:: 15928245

High prevalence of glucokinase mutations in Italian children with MODY. Influence on glucose tolerance, first-phase insulin response, insulin sensitivity and BMI.

Massa O, Meschi F, Cuesta-Munoz A, Caumo A, Cerutti F, Toni S, Cherubini V, Guazzarotti L, Sulli N, Matschinsky FM, Lorini R, Iafusco D, Barbetti F; Diabetes Study Group of the Italian Society of Paediatic Endocrinology and Diabetes (SIEDP)..

Diabetologia. 2001 Jul;44(7):898-905.

PubMed [citation]

PMID:: 11508276

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004295185.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 122 of the GCK protein (p.Leu122Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with maturity-onset diabetes of the young (MODY) (PMID: 15928245). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant disrupts the p.Leu122 amino acid residue in GCK. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11508276, 32468610). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

#	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: Sep 29, 2024

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