NM_000162.5(GCK):c.1148C>T (p.Ser383Leu) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Dec 10, 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:: RCV000420976.6

Allele description [Variation Report for NM_000162.5(GCK):c.1148C>T (p.Ser383Leu)]

NM_000162.5(GCK):c.1148C>T (p.Ser383Leu)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.1148C>T (p.Ser383Leu)

Other names:

NM_000162.5(GCK):c.1148C>T; p.Ser383Leu

HGVS:

NC_000007.14:g.44145602G>A
NG_008847.2:g.57569C>T
NM_000162.5:c.1148C>TMANE SELECT
NM_001354800.1:c.1148C>T
NM_001354801.1:c.137C>T
NM_001354802.1:c.8C>T
NM_001354803.2:c.182C>T
NM_033507.3:c.1151C>T
NM_033508.3:c.1145C>T
NP_000153.1:p.Ser383Leu
NP_001341729.1:p.Ser383Leu
NP_001341730.1:p.Ser46Leu
NP_001341731.1:p.Ser3Leu
NP_001341732.1:p.Ser61Leu
NP_277042.1:p.Ser384Leu
NP_277043.1:p.Ser382Leu
LRG_1074t1:c.1148C>T
LRG_1074t2:c.1151C>T
LRG_1074:g.57569C>T
LRG_1074p1:p.Ser383Leu
LRG_1074p2:p.Ser384Leu
NC_000007.13:g.44185201G>A
NM_000162.3:c.1148C>T
NM_033507.1:c.1151C>T
p.SER383LEU

Protein change:

S382L

Links:

dbSNP: rs777870079

NCBI 1000 Genomes Browser:

rs777870079

Molecular consequence:

NM_000162.5:c.1148C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.1148C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354801.1:c.137C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354802.1:c.8C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001354803.2:c.182C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.1151C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.1145C>T - missense variant - [Sequence Ontology: SO:0001583]

Functional consequence:

variation affecting protein function [Variation Ontology: 0003]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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VAMP8 vesicle associated membrane protein 8 [Canis lupus familiaris]
VAMP8 vesicle associated membrane protein 8 [Canis lupus familiaris]
Gene ID:609784

Gene
Mus musculus neurexin III (Nrxn3), transcript variant 3, mRNA
Mus musculus neurexin III (Nrxn3), transcript variant 3, mRNA
gi|433802865|ref|NM_001252074.2|

Nucleotide
Francisella noatunensis strain FSC1148, whole genome shotgun sequencing project
Francisella noatunensis strain FSC1148, whole genome shotgun sequencing project
gi|1954970751|gb|JACVKV000000000.1| V010000000

Nucleotide
Francisella noatunensis strain FSC1158 FSC1158_59_len1612, whole genome shotgun ...
Francisella noatunensis strain FSC1158 FSC1158_59_len1612, whole genome shotgun sequence
gi|1956169344|ref|NZ_JACVLE01000006 gnl|WGS:NZ_JACVLE01|FSC1158_59_len1612

Nucleotide
Pseudoloma neurophilia strain MK1 NODE_16983, whole genome shotgun sequence
Pseudoloma neurophilia strain MK1 NODE_16983, whole genome shotgun sequence
gi|948276164|gb|LGUB01001364.1||gnl LGUB01|NODE_16983

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000516034	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (May 24, 2021)	germline	clinical testing	Citation Link,
SCV000613403	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Likely pathogenic (Dec 21, 2016)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 24918535, 11942313, 12050210, 15841481, 16602010, 16963153, 17573900, 20337973, 21348868, 26467025
SCV003439540	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 10, 2023)	germline	clinical testing	PubMed (11) [See all records that cite these PMIDs] 12050210, 15841481, 17573900, 20337973, 22525692, 24918535, 28555465, 30447144, 30663027, 31216263, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000516034

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(May 24, 2021)

germline

clinical testing

Citation Link,

SCV000613403

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Likely pathogenic
(Dec 21, 2016)

germline

clinical testing

PubMed (10)
[See all records that cite these PMIDs]

SCV003439540

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 10, 2023)

germline

clinical testing

PubMed (11)
[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	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

To: Lindner T, Cockburn BN, Bell GI (1999). Molecular genetics of MODY in Germany. Diabetologia 42: 121-123.

Ziemssen F, Bellanné-Chantelot C, Osterhoff M, Schatz H, Pfeiffer AF.

Diabetologia. 2002 Feb;45(2):286-7; author reply 287-8. No abstract available.

PubMed [citation]

PMID:: 11942313

Aetiological heterogeneity of asymptomatic hyperglycaemia in children and adolescents.

Feigerlová E, Pruhová S, Dittertová L, Lebl J, Pinterová D, Kolostová K, Cerná M, Pedersen O, Hansen T.

Eur J Pediatr. 2006 Jul;165(7):446-52. Epub 2006 Apr 7.

PubMed [citation]

PMID:: 16602010

See all PubMed Citations (16)

Details of each submission

From GeneDx, SCV000516034.3

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 12050210, 32533152, 19790256, 14517946, 24918535, 17573900, 11942313, 28555465, 30663027, 21348868, 20337973, 16963153, 16602010, 15841481, 32375122, 31216263, 33242514, 32041611)

#	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

From Athena Diagnostics, SCV000613403.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

#	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 Invitae, SCV003439540.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (11)

Description

This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 383 of the GCK protein (p.Ser383Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of GCK-related conditions (PMID: 12050210, 15841481, 17573900, 20337973, 22525692, 24918535, 28555465, 30447144, 30663027, 31216263). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 236014). 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 with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.

#	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 7, 2024

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