Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| National Newborn Screening Laboratory, |
RCV002227424 | SCV002506577 | likely pathogenic | Maturity-onset diabetes of the young type 2 | criteria provided, single submitter | clinical testing | This is a nonsense variant in the GCK gene, where loss of function is a known mechanism of disease (PVS1). This variant results in a truncated protein by creating a premature stop codon. It is not present in population databases (GnomAD exomes, GnomAD genomes) (PM2). This variant has been reported in the literature associated with individuals with MODY2 (PMID: 30592380, 32375122) | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002509759 | SCV002819506 | pathogenic | Monogenic diabetes | 2022-12-13 | criteria provided, single submitter | clinical testing | Variant summary: GCK c.771G>A (p.Trp257X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 251090 control chromosomes (gnomAD). c.771G>A has been reported in the literature in individuals affected with Diabetes, MODY2 (Wang_2018, Zhou_2020, Ivanoshchuk_2021). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic. |
| Labcorp Genetics |
RCV003728049 | SCV004535420 | pathogenic | not provided | 2024-01-12 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Trp257*) in the GCK gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GCK are known to be pathogenic (PMID: 7553875, 9867845, 14578306, 24323243, 25015100). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hyperglycemia (PMID: 30592380). ClinVar contains an entry for this variant (Variation ID: 1679545). For these reasons, this variant has been classified as Pathogenic. |