Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV001289438 | SCV001477256 | uncertain significance | not provided | 2020-02-14 | criteria provided, single submitter | clinical testing | |
| Clinical Genomics, |
RCV003106181 | SCV002758758 | benign | 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 rs372405219 in MODY, yet. | |
| Labcorp Genetics |
RCV001289438 | SCV003030901 | likely benign | not provided | 2024-09-02 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003331107 | SCV004038227 | benign | not specified | 2023-08-05 | criteria provided, single submitter | clinical testing | Variant summary: GCK c.364-13G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: two predict the variant weakens a canonical 3' acceptor site, while one predicts the variant will have no significant impact on splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00013 in 250696 control chromosomes. The observed variant frequency is approximately 5.11 fold of the estimated maximal expected allele frequency for a pathogenic variant in GCK causing Monogenic Diabetes (2.5e-05), strongly suggesting that the variant is benign. c.364-13G>A has been reported in the literature in at least one control individual who was not affected with clinical features of GCK-related conditions (e.g., Siddiqui_2018). 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: 30386132). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014; one submitter classified the variant as likely benign, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as benign. |