NM_000162.5(GCK):c.951C>A (p.His317Gln) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: May 2, 2023
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:: RCV003704517.2

Allele description [Variation Report for NM_000162.5(GCK):c.951C>A (p.His317Gln)]

NM_000162.5(GCK):c.951C>A (p.His317Gln)

Gene:

GCK:glucokinase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p13

Genomic location:

Preferred name:

NM_000162.5(GCK):c.951C>A (p.His317Gln)

HGVS:

NC_000007.14:g.44146531G>T
NG_008847.2:g.56640C>A
NM_000162.5:c.951C>AMANE SELECT
NM_001354800.1:c.951C>A
NM_001354801.1:c.8+88C>A
NM_033507.3:c.954C>A
NM_033508.3:c.948C>A
NP_000153.1:p.His317Gln
NP_001341729.1:p.His317Gln
NP_277042.1:p.His318Gln
NP_277043.1:p.His316Gln
LRG_1074t1:c.951C>A
LRG_1074t2:c.954C>A
LRG_1074:g.56640C>A
LRG_1074p1:p.His317Gln
LRG_1074p2:p.His318Gln
NC_000007.13:g.44186130G>T

Protein change:

H316Q

Molecular consequence:

NM_001354801.1:c.8+88C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000162.5:c.951C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001354800.1:c.951C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033507.3:c.954C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_033508.3:c.948C>A - 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
SCV004461398	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (May 2, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31063852, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004461398

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(May 2, 2023)

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

GCK-MODY in the US Monogenic Diabetes Registry: Description of 27 unpublished variants.

Sanyoura M, Letourneau L, Knight Johnson AE, Del Gaudio D, Greeley SAW, Philipson LH, Naylor RN.

Diabetes Res Clin Pract. 2019 May;151:231-236. doi: 10.1016/j.diabres.2019.04.017. Epub 2019 May 4.

PubMed [citation]

PMID:: 31063852
PMCID:: PMC6544496

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004461398.1

#	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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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. A different variant (c.951C>G) giving rise to the same protein effect has been determined to be pathogenic (PMID: 31063852; Invitae). This suggests that this variant is also likely to be causative of disease. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 317 of the GCK protein (p.His317Gln).

#	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: Sep 29, 2024

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