NM_000162.5(GCK):c.728T>C (p.Leu243Pro) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 5, 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:: RCV001953519.6

Allele description [Variation Report for NM_000162.5(GCK):c.728T>C (p.Leu243Pro)]

NM_000162.5(GCK):c.728T>C (p.Leu243Pro)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.728T>C (p.Leu243Pro)

HGVS:

NC_000007.14:g.44147785A>G
NG_008847.2:g.55386T>C
NM_000162.5:c.728T>CMANE SELECT
NM_001354800.1:c.728T>C
NM_033507.3:c.731T>C
NM_033508.3:c.725T>C
NP_000153.1:p.Leu243Pro
NP_001341729.1:p.Leu243Pro
NP_277042.1:p.Leu244Pro
NP_277043.1:p.Leu242Pro
LRG_1074t1:c.728T>C
LRG_1074t2:c.731T>C
LRG_1074:g.55386T>C
LRG_1074p1:p.Leu243Pro
LRG_1074p2:p.Leu244Pro
NC_000007.13:g.44187384A>G

Protein change:

L242P

Links:

dbSNP: rs1470562535

NCBI 1000 Genomes Browser:

rs1470562535

Molecular consequence:

NM_000162.5:c.728T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.728T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.731T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.725T>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
SCV002241368	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 5, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22035297, 29056535, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002241368

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 5, 2023)

germline

clinical testing

PubMed (3)
[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

Doubling the referral rate of monogenic diabetes through a nationwide information campaign--update on glucokinase gene mutations in a Polish cohort.

Borowiec M, Fendler W, Antosik K, Baranowska A, Gnys P, Zmyslowska A, Malecki M, Mlynarski W.

Clin Genet. 2012 Dec;82(6):587-90. doi: 10.1111/j.1399-0004.2011.01803.x. Epub 2011 Dec 30.

PubMed [citation]

PMID:: 22035297

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 (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002241368.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 243 of the GCK protein (p.Leu243Pro). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individuals with autosomal dominant maturity-onset diabetes of the young (PMID: 22035297, 29056535; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1456947). 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 not expected to disrupt GCK protein function. For these reasons, this variant has been classified as Pathogenic.

#	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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