Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_000162.5(GCK):c.1169T>C (p.Ile390Thr)

CA213731

36184 (ClinVar)

Gene: GCK

Condition: monogenic diabetes

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 3ebec014-6469-4174-a9e8-90f4e74d1d75

HGVS expressions

NM_000162.5:c.1169T>C

NM_000162.5(GCK):c.1169T>C (p.Ile390Thr)

NC_000007.14:g.44145581A>G

CM000669.2:g.44145581A>G

NC_000007.13:g.44185180A>G

CM000669.1:g.44185180A>G

NC_000007.12:g.44151705A>G

NG_008847.1:g.48843T>C

NG_008847.2:g.57590T>C

ENST00000395796.8:c.*1167T>C

ENST00000616242.5:c.*289T>C

ENST00000683378.1:n.395T>C

ENST00000336642.9:c.203T>C

ENST00000345378.7:c.1172T>C

ENST00000403799.8:c.1169T>C

ENST00000671824.1:c.1232T>C

ENST00000672743.1:n.181T>C

ENST00000673284.1:c.1169T>C

ENST00000336642.8:c.221T>C

ENST00000345378.6:c.1172T>C

ENST00000395796.7:c.1166T>C

ENST00000403799.7:c.1169T>C

ENST00000437084.1:c.1118T>C

ENST00000459642.1:n.549T>C

ENST00000616242.4:c.1166T>C

NM_000162.3:c.1169T>C

NM_033507.1:c.1172T>C

NM_033508.1:c.1166T>C

NM_000162.4:c.1169T>C

NM_001354800.1:c.1169T>C

NM_001354801.1:c.158T>C

NM_001354802.1:c.29T>C

NM_001354803.1:c.203T>C

NM_033507.2:c.1172T>C

NM_033508.2:c.1166T>C

NM_033507.3:c.1172T>C

NM_033508.3:c.1166T>C

NM_001354803.2:c.203T>C

Uncertain Significance

PM2_Supporting PP3 PP2

Evidence Links 0

Expert Panel

Monogenic Diabetes VCEP

Criteria Specification Information

Criteria Specification: ClinGen Monogenic Diabetes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GCK Version 1.3.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.1169T>C variant in the glucokinase gene, GCK, causes an amino acid change of isoleucine to threonine at codon 390 (p.(Ile390Thr)) of NM_000162.5. GCK is defined by the ClinGen MDEP as a gene that has a low rate of benign missense variation and has pathogenic missense variants as a common mechanism of disease (PP2). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.878, which is greater than the MDEP VCEP threshold of 0.70 (PP3). In summary, c.1169T>C meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.3.0, approved 8/11/2023): PM2_supporting, PP2, PP3.

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_Supporting). gnomAD v4.0.0: absent

PP3

This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.878, which is greater than the MDEP VCEP threshold of 0.70 (PP3).

PP2

GCK is defined by the ClinGen MDEP as a gene that has a low rate of benign missense variation and has pathogenic missense variants as a common mechanism of disease (PP2).

Approved on: 2024-04-28

Published on: 2024-04-28

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