ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.758T>C (p.Val253Ala)

dbSNP: rs193921400
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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 RCV000029915 SCV000052570 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 RCV002472937 SCV002771537 uncertain significance not provided 2021-10-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002472937 SCV004295161 likely pathogenic not provided 2025-01-06 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 253 of the GCK protein (p.Val253Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant GCK-related conditions (PMID: 19790256, 36257325; internal data). ClinVar contains an entry for this variant (Variation ID: 36252). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt GCK protein function with a positive predictive value of 80%. This variant disrupts the p.Val253 amino acid residue in GCK. Other variant(s) that disrupt this residue have been observed in individuals with GCK-related conditions (PMID: 24735133, 25174781, 29056535), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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