NM_000162.5(GCK):c.1217T>C (p.Val406Ala) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 28, 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:: RCV003555324.2

Allele description [Variation Report for NM_000162.5(GCK):c.1217T>C (p.Val406Ala)]

NM_000162.5(GCK):c.1217T>C (p.Val406Ala)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.1217T>C (p.Val406Ala)

HGVS:

NC_000007.14:g.44145533A>G
NG_008847.2:g.57638T>C
NM_000162.5:c.1217T>CMANE SELECT
NM_001354800.1:c.1217T>C
NM_001354801.1:c.206T>C
NM_001354802.1:c.77T>C
NM_001354803.2:c.251T>C
NM_033507.3:c.1220T>C
NM_033508.3:c.1214T>C
NP_000153.1:p.Val406Ala
NP_001341729.1:p.Val406Ala
NP_001341730.1:p.Val69Ala
NP_001341731.1:p.Val26Ala
NP_001341732.1:p.Val84Ala
NP_277042.1:p.Val407Ala
NP_277043.1:p.Val405Ala
LRG_1074t1:c.1217T>C
LRG_1074t2:c.1220T>C
LRG_1074:g.57638T>C
LRG_1074p1:p.Val406Ala
LRG_1074p2:p.Val407Ala
NC_000007.13:g.44185132A>G

Protein change:

V26A

Molecular consequence:

NM_000162.5:c.1217T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.1217T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354801.1:c.206T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354802.1:c.77T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354803.2:c.251T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.1220T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.1214T>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
SCV004295128	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 28, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21348868, 19790256, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004295128

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 28, 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

Update on mutations in glucokinase (GCK), which cause maturity-onset diabetes of the young, permanent neonatal diabetes, and hyperinsulinemic hypoglycemia.

Osbak KK, Colclough K, Saint-Martin C, Beer NL, Bellanné-Chantelot C, Ellard S, Gloyn AL.

Hum Mutat. 2009 Nov;30(11):1512-26. doi: 10.1002/humu.21110. Review.

PubMed [citation]

PMID:: 19790256

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004295128.1

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

Description

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. This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 406 of the GCK protein (p.Val406Ala). 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 (PMID: 21348868). This variant disrupts the p.Val406 amino acid residue in GCK. Other variant(s) that disrupt this residue have been observed in individuals with GCK-related conditions (PMID: 19790256), which suggests that this may be a clinically significant amino acid residue. 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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