ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.1114G>T (p.Glu372Ter)

dbSNP: rs193922262
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Monogenic Diabetes Variant Curation Expert Panel RCV003493415 SCV004242345 likely pathogenic Monogenic diabetes 2024-01-22 reviewed by expert panel curation The c.1114G>T variant in the glucokinase gene, GCK, results in a premature termination at codon 372 (p.Glu372Ter) of NM_000162.5. While this variant, located in exon 9 of 10, is predicted to cause a premature stop codon and to escape nonsense mediated decay, it is in a functionally important region of a gene where loss-of-function is an established disease mechanism (PVS1). This variant is absent in gnomAD v2.1.1 (PM2_Supporting). This variant was identified in 3 unrelated individuals with hyperglycemia; however, PS4_Moderate cannot be applied because this number is below the ClinGen MDEP threshold (PMID: 22335469, ClinVar ID: 36174, internal lab contributor). Two of these individuals had a phenotype suggestive of GCK-hyperglycemia; however, PP4 is unable to be evaluated due to insufficient clinical information (PMID: 22335469, internal lab contributor). In summary, c.1114G>T meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.3.0, approved 8/11/2023): PVS1, PM2_supporting.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000029837 SCV000052492 likely pathogenic Maturity-onset diabetes of the young type 2 2011-08-18 criteria provided, single submitter curation Converted during submission to Likely pathogenic.

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