Submissions for variant NM_000162.5(GCK):c.982G>T (p.Gly328Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002376867	SCV002691128	pathogenic	Maturity onset diabetes mellitus in young	2020-08-07	criteria provided, single submitter	clinical testing	The p.G328* variant (also known as c.982G>T), located in coding exon 8 of the GCK gene, results from a G to T substitution at nucleotide position 982. This changes the amino acid from a glycine to a stop codon within coding exon 8. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003235717	SCV003934327	pathogenic	Monogenic diabetes	2023-05-09	criteria provided, single submitter	clinical testing	Variant summary: GCK c.982G>T (p.Gly328X) results in a premature termination codon, predicted to cause absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. Variants downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 245932 control chromosomes. To our knowledge, no occurrence of c.982G>T in individuals affected with Monogenic Diabetes and no experimental evidence demonstrating its impact on protein function have been reported. However, loss of function variants in the GCK gene are a well established mechanism of disease. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.