Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000429688 | SCV000521047 | likely pathogenic | not provided | 2016-10-05 | criteria provided, single submitter | clinical testing | The c.364-1 G>A splice site variant in the GCK gene has been previously reported in a patient with incidental hyperglycemia (Lorini et al., 2009). This variant destroys the canonical splice acceptor site in intron 3, and is expected to cause abnormal gene splicing. However, the adjacent exon 4 is predicted to remain in frame. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown. Additionally, the variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we consider this variant to be likely pathogenic. |
Athena Diagnostics Inc | RCV000429688 | SCV000613424 | pathogenic | not provided | 2021-04-29 | criteria provided, single submitter | clinical testing | This variant is expected to severely impact normal RNA splicing, and consequently, protein structure and/or function. 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. |
Clinical Genomics, |
RCV002450985 | SCV002605275 | 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 rs1057521094 in MODY, yet. | |
Ambry Genetics | RCV002450985 | SCV002613759 | pathogenic | Maturity onset diabetes mellitus in young | 2017-05-17 | criteria provided, single submitter | clinical testing | The c.364-1G>A intronic pathogenic mutation results from a G to A substitution one nucleotide upstream from coding exon 4 of the GCK gene. This variant was identified in multiple families with maturity-onset diabetes of the young (Osbak KK et al. Hum. Mutat., 2009 Nov;30:1512-26). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as likely pathogenic. |