U.S. flag

An official website of the United States government

NM_000162.5(GCK):c.397T>C (p.Phe133Leu) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 25, 2022
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:
RCV001844289.1

Allele description [Variation Report for NM_000162.5(GCK):c.397T>C (p.Phe133Leu)]

NM_000162.5(GCK):c.397T>C (p.Phe133Leu)

Gene:
GCK:glucokinase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p13
Genomic location:
Preferred name:
NM_000162.5(GCK):c.397T>C (p.Phe133Leu)
HGVS:
  • NC_000007.14:g.44151042A>G
  • NG_008847.2:g.52129T>C
  • NM_000162.5:c.397T>CMANE SELECT
  • NM_001354800.1:c.397T>C
  • NM_033507.3:c.400T>C
  • NM_033508.3:c.394T>C
  • NP_000153.1:p.Phe133Leu
  • NP_001341729.1:p.Phe133Leu
  • NP_277042.1:p.Phe134Leu
  • NP_277043.1:p.Phe132Leu
  • LRG_1074t1:c.397T>C
  • LRG_1074t2:c.400T>C
  • GRCH37chr7:g.44190641A>G
  • LRG_1074:g.52129T>C
  • LRG_1074p1:p.Phe133Leu
  • LRG_1074p2:p.Phe134Leu
  • NC_000007.13:g.44190641A>G
  • NM_000162.3:c.397T>C
Protein change:
F132L
Links:
dbSNP: rs2128822093
NCBI 1000 Genomes Browser:
rs2128822093
Molecular consequence:
  • NM_000162.5:c.397T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354800.1:c.397T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033507.3:c.400T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033508.3:c.394T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002103380Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Feb 25, 2022) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Molecular genetic testing of patients with monogenic diabetes and hyperinsulinism.

Bennett JT, Vasta V, Zhang M, Narayanan J, Gerrits P, Hahn SH.

Mol Genet Metab. 2015 Mar;114(3):451-8. doi: 10.1016/j.ymgme.2014.12.304. Epub 2014 Dec 20.

PubMed [citation]
PMID:
25555642
PMCID:
PMC7852340

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002103380.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

Variant summary: GCK c.397T>C (p.Phe133Leu) results in a non-conservative amino acid change located in the Hexokinase, N-terminal domain (IPR022672) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. A different nucleotide change, c.398T>A (p.Phe133Tyr) affecting the same location has also been reported with an associated phenotype of MODY2 in the HGMD database supporting the functional relevance of this residue to overall protein function. The variant was absent in 251362 control chromosomes. c.397T>C has been reported in the literature as a likely pathogenic variant in at-least one individual reportedly affected with Maturity Onset Diabetes Of The Young in a referral laboratory cohort (example, Bennett_2015). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The same clinical diagnostic laboratory reporting this variant has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 20, 2024