Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000029861 | SCV000052516 | 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 | RCV001288979 | SCV001476454 | likely pathogenic | not provided | 2020-02-25 | criteria provided, single submitter | clinical testing | Not found in the total gnomAD dataset, and the data is high quality. Predicted to have a damaging effect on the protein. One other pathogenic or likely pathogenic variant affects the same amino acid. Segregation with disease in affected individuals from a single family. |
| Invitae | RCV001288979 | SCV002238454 | pathogenic | not provided | 2021-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glycine at codon 447 of the GCK protein (p.Arg447Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 36198). This missense change has been observed in individuals with autosomal recessive permanent neonatal diabetes mellitus and autosomal dominant MODY (PMID: 26587058; Invitae). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). |
| Ambry Genetics | RCV002381268 | SCV002691878 | pathogenic | Maturity onset diabetes mellitus in young | 2017-05-19 | criteria provided, single submitter | clinical testing | The p.R447G pathogenic mutation (also known as c.1339C>G), located in coding exon 10 of the GCK gene, results from a C to G substitution at nucleotide position 1339. The arginine at codon 447 is replaced by glycine, an amino acid with dissimilar properties. This mutation was paternally inherited in two Brazilian double first cousins with permanent neonatal diabetes mellitus; each had a second, maternally inherited GCK alteration in trans. Their heterozygous fathers exhibited a maturity-onset diabetes of the young (MODY) phenotype (Esquiaveto-Aun AM et al. Diabetol Metab Syndr, 2015 Nov;7:101). In addition, another disease-causing alteration, p.R447Q, has been described in the same codon (Pruhova S et al. Pediatr Diabetes, 2010 Dec;11:529-35). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |