Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genetics and Molecular Pathology, |
RCV003447825 | SCV004175653 | likely pathogenic | Maturity-onset diabetes of the young type 2 | 2022-12-09 | criteria provided, single submitter | clinical testing | The GCK c.554T>C variant is classified as Likely Pathogenic (PM2, PP3, PM1, PP1). The GCK c.554T>C variant is a single nucleotide change in exon 5/10 of the GCK gene, which is predicted to change the amino acid leucine at position 185 in the protein to proline. This variant is absent from population databases and has not been reported in dbSNP or ClinVar (PM2). This variant is reported in HGMD as disease causing (CM195845). Computational predictions support a deleterious effect on the gene or gene product (PP3). This variant is a novel missense change at an amino acid residue where three different missense changes have been seen before in association with diabetes-MODY and pre-gestational diabetes) (PM1). This variant has been reported as likely pathogenic in one family with affected three members (PMID 31063852). The authors also reported a different missense variant at the same amino acid residue (p.L185R) as likely pathogenic in one family with one affected member (PMID 31063852). Another missense variant at the same amino acid residue (p.L185V) has also been reported as likely pathogenic in 2 unrelated individuals with gestational diabetes (PMID 30663027) (PP1). |