Submissions for variant NM_000162.5(GCK):c.940C>A (p.Leu314Met)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV005052357	SCV005685568	uncertain significance	not provided	2024-07-24	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV005052357	SCV005751804	uncertain significance	not provided	2024-04-16	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 314 of the GCK protein (p.Leu314Met). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GCK-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt GCK protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.