NM_000162.5(GCK):c.926T>C (p.Leu309Pro) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 18, 2020
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:: RCV001817944.4

Allele description [Variation Report for NM_000162.5(GCK):c.926T>C (p.Leu309Pro)]

NM_000162.5(GCK):c.926T>C (p.Leu309Pro)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.926T>C (p.Leu309Pro)

HGVS:

NC_000007.14:g.44146556A>G
NG_008847.2:g.56615T>C
NM_000162.5:c.926T>CMANE SELECT
NM_001354800.1:c.926T>C
NM_001354801.1:c.8+63T>C
NM_033507.3:c.929T>C
NM_033508.3:c.923T>C
NP_000153.1:p.Leu309Pro
NP_001341729.1:p.Leu309Pro
NP_277042.1:p.Leu310Pro
NP_277043.1:p.Leu308Pro
LRG_1074t1:c.926T>C
LRG_1074t2:c.929T>C
LRG_1074:g.56615T>C
LRG_1074p1:p.Leu309Pro
LRG_1074p2:p.Leu310Pro
NC_000007.13:g.44186155A>G
NM_000162.3:c.926T>C

Protein change:

L308P

Links:

dbSNP: rs2128820009

NCBI 1000 Genomes Browser:

rs2128820009

Molecular consequence:

NM_001354801.1:c.8+63T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000162.5:c.926T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.926T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.929T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.923T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

LOC117837391 [Setaria viridis]
LOC117837391 [Setaria viridis]
Gene ID:117837391

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002067458	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 18, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002067458

Genetic Services Laboratory, University of Chicago

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 18, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Genetic Services Laboratory, University of Chicago, SCV002067458.1

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

Description

This sequence change is absent from known population databases (gnomAD). The p.Leu309Pro change affects a highly conserved amino acid residue located in a domain of the GCK protein that is known to be functional. The p.Leu309Pro substitution appears to be deleterious using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This sequence change has been previously reported in individuals with GCK-related hyperglycemia (PMID: 8433729). Functional studies demonstrated a reduction in enzyme activity (PMIDs:10525657, 8446612, 29704611). Furthermore, other amino acid substitutions at this same positon (p.Leu309Val, Leu309His) have also been reported in patients with GCK-related hyperglycemia (PMIDs: 19790256, 28323911). Collectively, these evidences indicate that this sequence change is pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 24, 2023

ClinVar

Relating variation to medicine