Description
DNA sequence analysis of the GCK gene demonstrated a sequence change, c.617C>T, in exon 6 that results in an amino acid change, p.Thr206Met. The p.Thr206Met change affects a highly conserved amino acid residue located in a domain of the GCK protein that is known to be functional. The p.Thr206Met substitution appears to be deleterious using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). The p.Thr206Met sequence change has previously been described in multiple patients with GCK-related maturity onset diabetes of the young (MODY) (PMIDs: 24606082, 2014, 11508276). Several other pathogenic sequence changes affecting the same p.Thr206 amino acid (p.Thr206Arg, p.Thr206Lys, p.Thr206Ala, and p.Thr206Pro) have been reported in patients with GCK-MODY (PMIDs: 19790256, 17937063, 12442280, 24405491). Furthermore, functional studies of the p.Thr206Met sequence change demonstrated that it results in severe loss of function (PMID: 24606082).
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |