NM_000162.5(GCK):c.1129C>A (p.Arg377Ser) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 17, 2021
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:: RCV003102308.3

Allele description [Variation Report for NM_000162.5(GCK):c.1129C>A (p.Arg377Ser)]

NM_000162.5(GCK):c.1129C>A (p.Arg377Ser)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.1129C>A (p.Arg377Ser)

Other names:

NM_000162.5(GCK):c.1129C>A; p.Arg377Ser

HGVS:

NC_000007.14:g.44145621G>T
NG_008847.2:g.57550C>A
NM_000162.5:c.1129C>AMANE SELECT
NM_001354800.1:c.1129C>A
NM_001354801.1:c.118C>A
NM_001354802.1:c.-12C>A
NM_001354803.2:c.163C>A
NM_033507.3:c.1132C>A
NM_033508.3:c.1126C>A
NP_000153.1:p.Arg377Ser
NP_001341729.1:p.Arg377Ser
NP_001341730.1:p.Arg40Ser
NP_001341732.1:p.Arg55Ser
NP_277042.1:p.Arg378Ser
NP_277043.1:p.Arg376Ser
LRG_1074t1:c.1129C>A
LRG_1074t2:c.1132C>A
LRG_1074:g.57550C>A
LRG_1074p1:p.Arg377Ser
LRG_1074p2:p.Arg378Ser
NC_000007.13:g.44185220G>T
NM_000162.3:c.1129C>A

Protein change:

R376S

Molecular consequence:

NM_001354802.1:c.-12C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000162.5:c.1129C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.1129C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354801.1:c.118C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354803.2:c.163C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.1132C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.1126C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Gymnocactus saueri (17)
Nucleotide
Uncultured bacterium clone OTU_8579 16S ribosomal RNA gene, partial sequence
Uncultured bacterium clone OTU_8579 16S ribosomal RNA gene, partial sequence
gi|1496546217|gb|MH532227.1|

Nucleotide
Uncultured bacterium clone OTU_7176 16S ribosomal RNA gene, partial sequence
Uncultured bacterium clone OTU_7176 16S ribosomal RNA gene, partial sequence
gi|1496544814|gb|MH530824.1|

Nucleotide
SNF2/RAD54 family (ETL1 subfamily) protein [Arabidopsis thaliana]
SNF2/RAD54 family (ETL1 subfamily) protein [Arabidopsis thaliana]
gi|27311941|gb|AAO00936.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003439928	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 17, 2021)	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

SCV003439928

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 17, 2021)

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003439928.2

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

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This missense change has been observed in individual(s) with maturity-onset diabetes of the young (PMID: 19790256). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 377 of the GCK protein (p.Arg377Ser).

#	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: May 1, 2024

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