ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.351_358del (p.Thr118fs)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Geisinger Clinic, Geisinger Health System RCV002285556 SCV002562169 pathogenic Maturity-onset diabetes of the young type 2 2022-08-02 criteria provided, single submitter research PVS1, PM2, PP1, PS4_Moderate, PP4
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV004017919 SCV004848496 likely pathogenic Maturity onset diabetes mellitus in young 2020-11-06 criteria provided, single submitter clinical testing The p.Thr117AspfsX8 variant in GCK has not been reported in individuals with maturity-onset diabetes of the young (MODY) and was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 117 and leads to a premature termination codon 8 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the GCK gene is an established disease mechanism in maturity-onset diabetes of the young. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal dominant MODY. ACMG/AMP Criteria applied: PVS1, PM2.

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