Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000734686 | SCV000862845 | pathogenic | not provided | 2018-08-20 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000734686 | SCV002217154 | pathogenic | not provided | 2022-01-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. ClinVar contains an entry for this variant (Variation ID: 598320). This premature translational stop signal has been observed in individual(s) with autosomal dominant maturity-onset diabetes of the young (PMID: 30592380). This variant is not present in population databases (gnomAD no frequency). 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). |
| Clinical Genomics, |
RCV002463737 | SCV002605072 | pathogenic | Maturity onset diabetes mellitus in young | criteria provided, single submitter | research | Potent mutations in GCK gene is associated with poor secretion of insulin. Its associated with milder forms of diabetes, which can be controlled by diet . However, there is no sufficient evidence to ascertain the significance of rs1562715426 in MODY, yet. | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003987690 | SCV004804307 | pathogenic | Maturity-onset diabetes of the young type 2 | 2024-01-09 | criteria provided, single submitter | clinical testing | Variant summary: GCK c.770G>A (p.Trp257X) results in a premature termination codon and is predicted to cause absence of the protein due to nonsense mediated decay, a commonly known mechanism for disease. The variant was absent in 251090 control chromosomes (gnomAD). c.770G>A has been reported in the literature in at least one individual affected with Maturity Onset Diabetes Of The Young 2/Neonatal Diabetes Mellitus (e.g. Mirshahi_2022). These data suggest the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 36257325). ClinVar contains an entry for this variant (Variation ID: 598320). Based on the evidence outlined above, the variant was classified as pathogenic. |