Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000029843 | SCV000052498 | likely pathogenic | Maturity-onset diabetes of the young type 2 | 2011-08-18 | criteria provided, single submitter | curation | Converted during submission to Likely pathogenic. |
Athena Diagnostics Inc | RCV000517698 | SCV000613405 | likely pathogenic | not provided | 2022-11-04 | criteria provided, single submitter | clinical testing | This variant has been identified in at least one individual with clinical features associated with MODY, including a de novo case. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Computational tools predict that this variant is damaging. |
Clinical Genomics, |
RCV002285137 | SCV002574771 | uncertain significance | 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 well. However, there is no sufficient evidence to assertain the significance of rs193922268 in MODY, yet. This variant is shown to be potentially damaging by in silico analysis. | |
Invitae | RCV000517698 | SCV004422867 | uncertain significance | not provided | 2023-02-23 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 386 of the GCK protein (p.Leu386Pro). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GCK-related conditions. ClinVar contains an entry for this variant (Variation ID: 36180). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GCK protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |