Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV003564073 | SCV004315483 | uncertain significance | not provided | 2023-08-24 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 177 of the GCK protein (p.Glu177Asp). 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. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with clinical features of GCK-related conditions (PMID: 22941762, 30663027; Invitae). It has also been observed to segregate with disease in related individuals. 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 not expected to disrupt GCK protein function. |
| Athena Diagnostics | RCV003564073 | SCV005622470 | likely pathogenic | not provided | 2024-05-03 | criteria provided, single submitter | clinical testing | 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 tested at Athena Diagnostics with clinical features associated with this gene. Assessment of experimental evidence suggests this variant results in abnormal protein function. PMID: 37101203 |