ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.107G>A (p.Arg36Gln)

gnomAD frequency: 0.00001  dbSNP: rs193922261
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV001249065 SCV001423012 uncertain significance Maturity-onset diabetes of the young type 2 2020-01-22 criteria provided, single submitter curation The p.Arg36Gln variant in GCK has not been previously reported in individuals with maturity-onset diabetes of the young but has been identified in 0.003% (1/30616) of South Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs193922261). Please note that for diseases with clinical variability, or reduced penetrance, pathogenic variants may be present at a low frequency in the general population. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Arg36Gln variant is uncertain. ACMG/AMP Criteria applied: PM2 (Richards 2015).
Labcorp Genetics (formerly Invitae), Labcorp RCV001879749 SCV002289362 uncertain significance not provided 2021-11-27 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 972809). 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. This variant disrupts the p.Arg36 amino acid residue in GCK. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8168652, 17573900, 21348868, 22493702; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant is also known as p.Arg37Gln. This missense change has been observed in individual(s) with maturity-onset diabetes of the young (PMID: 19790256, 28663157). This variant is present in population databases (no rsID available, gnomAD 0.003%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 36 of the GCK protein (p.Arg36Gln).
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002464037 SCV002605426 uncertain risk allele Maturity onset diabetes mellitus in young criteria provided, single submitter research Potent mutations in GCK gene is associated with poor secretion of insulin. Its associated with milder forms of diabetes, which can be controlled by diet . However, there is no sufficient evidence to ascertain the significance of rs193922261 in MODY, yet.
Fulgent Genetics, Fulgent Genetics RCV002485984 SCV002787085 uncertain significance Type 2 diabetes mellitus; Hyperinsulinism due to glucokinase deficiency; Maturity-onset diabetes of the young type 2; Permanent neonatal diabetes mellitus 1 2021-08-09 criteria provided, single submitter clinical testing

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