ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.1367C>T (p.Ala456Val)

dbSNP: rs104894014
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV001818166 SCV002069051 pathogenic not provided 2017-12-12 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001818166 SCV004295117 pathogenic not provided 2023-01-28 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 456 of the GCK protein (p.Ala456Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hyperinsulinemic hypoglycemia (PMID: 11916951, 14687251). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 16143). 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. Experimental studies have shown that this missense change affects GCK function (PMID: 11916951, 15987895, 17082186, 17353190, 19146401, 21831042, 22194744). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000017525 SCV000037797 pathogenic Hyperinsulinism due to glucokinase deficiency 2002-04-01 no assertion criteria provided literature only

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