Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002421967 | SCV002725600 | pathogenic | Maturity onset diabetes mellitus in young | 2018-12-30 | criteria provided, single submitter | clinical testing | The c.1077delC pathogenic mutation, located in coding exon 9 of the GCK gene, results from a deletion of one nucleotide at nucleotide position 1077, causing a translational frameshift with a predicted alternate stop codon (p.S360Rfs*42). This frameshift occurs at the 3' terminus of GCK, is not expected to trigger nonsense-mediated mRNA decay, and impacts only the last 107 amino acids of the protein. The exact functional impact of these altered amino acids is unknown at this time. However, there are multiple pathogenic mutations reported in the 3' end of GCK (Osbak KK et al. Hum. Mutat., 2009 Nov;30:1512-26). In addition, some of the altered residues are located at the ATP-binding site of the GCK protein (Molnes J et al. FEBS J., 2011 Jul;278:2372-86). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |