NM_000162.5(GCK):c.834C>A (p.Asp278Glu) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 15, 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:: RCV003555334.2

Allele description [Variation Report for NM_000162.5(GCK):c.834C>A (p.Asp278Glu)]

NM_000162.5(GCK):c.834C>A (p.Asp278Glu)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.834C>A (p.Asp278Glu)

HGVS:

NC_000007.14:g.44147679G>T
NG_008847.2:g.55492C>A
NM_000162.5:c.834C>AMANE SELECT
NM_001354800.1:c.834C>A
NM_033507.3:c.837C>A
NM_033508.3:c.831C>A
NP_000153.1:p.Asp278Glu
NP_001341729.1:p.Asp278Glu
NP_277042.1:p.Asp279Glu
NP_277043.1:p.Asp277Glu
LRG_1074t1:c.834C>A
LRG_1074t2:c.837C>A
LRG_1074:g.55492C>A
LRG_1074p1:p.Asp278Glu
LRG_1074p2:p.Asp279Glu
NC_000007.13:g.44187278G>T

Protein change:

D277E

Molecular consequence:

NM_000162.5:c.834C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.834C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.837C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.831C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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PTGES [Taeniopygia guttata]
PTGES [Taeniopygia guttata]
Gene ID:100226316

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004295157	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 15, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21348868, 28862987, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004295157

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 15, 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

Novel glucokinase mutations in patients with monogenic diabetes - clinical outline of GCK-MD and potential for founder effect in Slavic population.

Borowiec M, Antosik K, Fendler W, Deja G, Jarosz-Chobot P, Mysliwiec M, Zmyslowska A, Malecki M, Szadkowska A, Mlynarski W.

Clin Genet. 2012 Mar;81(3):278-83. doi: 10.1111/j.1399-0004.2011.01656.x. Epub 2011 Mar 18.

PubMed [citation]

PMID:: 21348868

MODY in Ukraine: genes, clinical phenotypes and treatment.

Globa E, Zelinska N, Elblova L, Dusatkova P, Cinek O, Lebl J, Colclough K, Ellard S, Pruhova S.

J Pediatr Endocrinol Metab. 2017 Oct 26;30(10):1095-1103. doi: 10.1515/jpem-2017-0075.

PubMed [citation]

PMID:: 28862987

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004295157.1

#	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 aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 278 of the GCK protein (p.Asp278Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant maturity onset diabetes of the young and autosomal recessive premature neonatal diabetes mellitus (PMID: 21348868, 28862987; Invitae). It has also been observed to segregate with disease in related individuals. 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 with a positive predictive value of 80%. 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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