NM_000162.5(GCK):c.1156C>G (p.Leu386Val) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 16, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000992039.4

Allele description [Variation Report for NM_000162.5(GCK):c.1156C>G (p.Leu386Val)]

NM_000162.5(GCK):c.1156C>G (p.Leu386Val)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.1156C>G (p.Leu386Val)

Other names:

NM_000162.5(GCK):c.1156C>G; p.Leu386Val

HGVS:

NC_000007.14:g.44145594G>C
NG_008847.2:g.57577C>G
NM_000162.5:c.1156C>GMANE SELECT
NM_001354800.1:c.1156C>G
NM_001354801.1:c.145C>G
NM_001354802.1:c.16C>G
NM_001354803.2:c.190C>G
NM_033507.3:c.1159C>G
NM_033508.3:c.1153C>G
NP_000153.1:p.Leu386Val
NP_001341729.1:p.Leu386Val
NP_001341730.1:p.Leu49Val
NP_001341731.1:p.Leu6Val
NP_001341732.1:p.Leu64Val
NP_277042.1:p.Leu387Val
NP_277043.1:p.Leu385Val
LRG_1074t1:c.1156C>G
LRG_1074t2:c.1159C>G
LRG_1074:g.57577C>G
LRG_1074p1:p.Leu386Val
LRG_1074p2:p.Leu387Val
NC_000007.13:g.44185193G>C
NC_000007.13:g.44185193G>C
NM_000162.3:c.1156C>G

Protein change:

L385V

Links:

dbSNP: rs1583591700

NCBI 1000 Genomes Browser:

rs1583591700

Molecular consequence:

NM_000162.5:c.1156C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.1156C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354801.1:c.145C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354802.1:c.16C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354803.2:c.190C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.1159C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.1153C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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vitamin D 25-hydroxylase isoform 1 [Homo sapiens]
vitamin D 25-hydroxylase isoform 1 [Homo sapiens]
gi|45267826|ref|NP_078790.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001144003	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Uncertain significance (Apr 30, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19790256, 26467025
SCV004295136	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 16, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19790256, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001144003

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Uncertain significance
(Apr 30, 2019)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV004295136

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 16, 2023)

germline

clinical testing

PubMed (2)
[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

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

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 Athena Diagnostics, SCV001144003.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004295136.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 386 of the GCK protein (p.Leu386Val). This variant is not present in population databases (gnomAD no frequency). 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. 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. ClinVar contains an entry for this variant (Variation ID: 804837). This missense change has been observed in individual(s) with maturity onset diabetes of the young (PMID: 19790256).

#	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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