Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004689428 | SCV000052581 | pathogenic | Monogenic diabetes | 2024-05-21 | criteria provided, single submitter | clinical testing | Variant summary: GCK c.871A>T (p.Lys291X) 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. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. c.871A>T has been reported in the literature in at-least one individual affected with Monogenic Diabetes (example: Bansal_2017). The following publication has been ascertained in the context of this evaluation (PMID: 29207974). ClinVar contains an entry for this variant (Variation ID: 36263). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Gene |
RCV000521942 | SCV000622011 | pathogenic | not provided | 2024-02-01 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: Deng2023[preprint], 36257325, 29207974) |
| Labcorp Genetics |
RCV000521942 | SCV002241987 | pathogenic | not provided | 2023-10-04 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys291*) 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 early onset diabetes mellitus (PMID: 29207974). ClinVar contains an entry for this variant (Variation ID: 36263). For these reasons, this variant has been classified as Pathogenic. |
| Clinical Genomics, |
RCV002285138 | SCV002574767 | pathogenic | Diabetes mellitus | 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 well. c.871A>T / rs193922335 variant in particular is found to be pathogenic for monogenic diabetes. | |
| Athena Diagnostics | RCV000521942 | SCV002771539 | pathogenic | not provided | 2022-01-13 | criteria provided, single submitter | clinical testing | This variant is expected to result in the loss of a functional protein. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). This variant has been identified in at least one individual with clinical features associated with this gene. |
| Fulgent Genetics, |
RCV002490414 | SCV002781703 | likely pathogenic | Type 2 diabetes mellitus; Hyperinsulinism due to glucokinase deficiency; Maturity-onset diabetes of the young type 2; Permanent neonatal diabetes mellitus 1 | 2021-07-16 | criteria provided, single submitter | clinical testing |