Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV003480802 | SCV004223872 | likely pathogenic | Monogenic diabetes | 2023-12-08 | reviewed by expert panel | curation | The c.466C>T variant in the glucokinase gene, GCK, causes an amino acid change of histidine to tyrosine at codon 156 (p.(His156Tyr)) of NM_000162.5. This variant was identified in an individual with a clinical history highly specific for GCK-hyperglycemia (FBG 5.5-8 mmol/L and HbA1c 5.6 - 7.6% and OGTT increment < 3 mmol/L) (PP4_Moderate; internal lab contributors). This variant segregated with diabetes/hyperglycemia, with 2 informative meioses in 2 families (PP1; internal lab contributors). GCK is defined by the ClinGen MDEP as a gene that has a low rate of benign missense variation and has pathogenic missense variants as a common mechanism of disease (PP2). This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.88 which is greater than the MDEP VCEP threshold of 0.70 (PP3). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). In summary, c.466C>T meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.3.0, approved 8/12/2023): PP4_Moderate, PP1, PP2, PP3, PM2_Supporting. |
| Athena Diagnostics Inc | RCV000711775 | SCV000842171 | uncertain significance | not provided | 2017-09-13 | criteria provided, single submitter | clinical testing | |
| Clinical Genomics, |
RCV002464031 | SCV002605246 | likely 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 rs1562718043 in MODY, yet. |