ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.1391del (p.Gly464fs)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Monogenic Diabetes Variant Curation Expert Panel RCV003313352 SCV004012118 likely pathogenic Monogenic diabetes 2023-06-18 reviewed by expert panel curation The c.1391del variant in the glucokinase gene, GCK, causes a frameshift in the protein at codon 464 (NM_000162.5), adding 150 novel amino acids before encountering a stop codon (p.(Gly464AlafsTer150)). This variant, located in exon 10 of 10, is predicted to cause loss of a stop codon and result in an elongated protein. The additional residues are expected to cause improper folding, resulting in loss of function in a gene in which loss-of-function is an established disease mechanism (PVS1; PMID 19790256). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, c.1391del meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.2.0, approved 6/7/2023): PVS1, PM2_Supporting

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