ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.704T>C (p.Met235Thr)

dbSNP: rs193922323
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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 RCV000029911 SCV000052566 likely pathogenic Maturity-onset diabetes of the young type 2 2011-08-18 criteria provided, single submitter curation Converted during submission to Likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003556090 SCV004295165 uncertain significance not provided 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 235 of the GCK protein (p.Met235Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with maturity-onset diabetes of the young (PMID: 14517946). ClinVar contains an entry for this variant (Variation ID: 36248). 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%. This variant disrupts the p.Met235 amino acid residue in GCK. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 17186219, 24323243). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Centre for Inherited Metabolic Diseases, Karolinska University Hospital RCV000029911 SCV004808512 pathogenic Maturity-onset diabetes of the young type 2 2024-04-04 criteria provided, single submitter clinical testing

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