NM_000162.5(GCK):c.1340G>C (p.Arg447Pro) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Feb 7, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV000992046.3

Allele description [Variation Report for NM_000162.5(GCK):c.1340G>C (p.Arg447Pro)]

NM_000162.5(GCK):c.1340G>C (p.Arg447Pro)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.1340G>C (p.Arg447Pro)

HGVS:

NC_000007.14:g.44145194C>G
NG_008847.2:g.57977G>C
NM_000162.5:c.1340G>CMANE SELECT
NM_001354800.1:c.1340G>C
NM_001354801.1:c.329G>C
NM_001354802.1:c.200G>C
NM_001354803.2:c.374G>C
NM_033507.3:c.1343G>C
NM_033508.3:c.1337G>C
NP_000153.1:p.Arg447Pro
NP_001341729.1:p.Arg447Pro
NP_001341730.1:p.Arg110Pro
NP_001341731.1:p.Arg67Pro
NP_001341732.1:p.Arg125Pro
NP_277042.1:p.Arg448Pro
NP_277043.1:p.Arg446Pro
LRG_1074t1:c.1340G>C
LRG_1074t2:c.1343G>C
LRG_1074:g.57977G>C
LRG_1074p1:p.Arg447Pro
LRG_1074p2:p.Arg448Pro
NC_000007.13:g.44184793C>G
NM_000162.3:c.1340G>C

Protein change:

R110P

Links:

dbSNP: rs1131691416

NCBI 1000 Genomes Browser:

rs1131691416

Molecular consequence:

NM_000162.5:c.1340G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.1340G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354801.1:c.329G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354802.1:c.200G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354803.2:c.374G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.1343G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.1337G>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
SCV001144010	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Uncertain significance (Jul 11, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23890519, 26467025
SCV005201992	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Feb 7, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001144010

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Uncertain significance
(Jul 11, 2019)

germline

clinical testing

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

SCV005201992

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Feb 7, 2024)

germline

clinical testing

Citation Link

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
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A report of 2 new cases of MODY2 and review of the literature: implications in the search for type 2 diabetes drugs.

Shammas C, Neocleous V, Phelan MM, Lian LY, Skordis N, Phylactou LA.

Metabolism. 2013 Nov;62(11):1535-42. doi: 10.1016/j.metabol.2013.06.007. Epub 2013 Jul 24. Review.

PubMed [citation]

PMID:: 23890519

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

Details of each submission

From Athena Diagnostics, SCV001144010.1

#	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 GeneDx, SCV005201992.1

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; This variant is associated with the following publications: (PMID: 26587058, 34440516, 23890519)

#	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: Sep 29, 2024

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