ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.952G>T (p.Gly318Trp)

gnomAD frequency: 0.00001  dbSNP: rs193922340
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000029931 SCV000052586 likely pathogenic Maturity-onset diabetes of the young type 2 2011-08-18 criteria provided, single submitter curation Converted during submission to Likely pathogenic.
Ambry Genetics RCV002371789 SCV002686784 likely pathogenic Maturity onset diabetes mellitus in young 2016-02-06 criteria provided, single submitter clinical testing The p.G318W variant (also known as c.952G>T), located in coding exon 8 of the GCK gene, results from a G to T substitution at nucleotide position 952. The glycine at codon 318 is replaced by tryptophan, an amino acid with highly dissimilar properties. This variant results in perturbation of the structure as much as known pathogenic variants (Zhang, R., Zhou, M., Peterson, S., Anderson, W., Joachimiak, A. The crystal structure of the adenylosuccinate synthetase from Yersinia pestis CO92. PDB ID: 3HID. http://www.rcsb.org/pdb/explore/explore.do?structureId=3HID). This variant was previously reported in the SNPDatabase as rs193922340. Based on data from the NHLBI Exome Sequencing Project (ESP), no alterations were observed among 13006 alleles tested (0.0%). Allele frequency data for this nucleotide position is not currently available from the 1000 Genomes Project. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Athena Diagnostics RCV002472939 SCV002771541 likely pathogenic not provided 2024-12-02 criteria provided, single submitter clinical testing The frequency of this variant in the general population is consistent with pathogenicity. (http://gnomad.broadinstitute.org) This variant has been identified in at least one individual with clinical features of MODY. Assessment of experimental evidence suggests this variant results in abnormal protein function. (PMID: 37101203) At least one other missense variant at this codon is considered to be pathogenic or likely pathogenic, suggesting this variant may also cause disease.

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