ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.214G>A (p.Gly72Arg) (rs193922289)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000255585 SCV000842164 pathogenic not provided 2018-07-12 criteria provided, single submitter clinical testing
GeneDx RCV000255585 SCV000321712 pathogenic not provided 2018-09-18 criteria provided, single submitter clinical testing The G72R variant has been published previously in association with MODY2 (Lehto et al., 1999; Flanagan et al., 2014; Raimondo et al., 2014; Agladioglu et al., 2015). The variant was not observed at any significant frequency in large population cohorts (Lek et al., 2016). G72R is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position within a connecting region that is conserved across species, and which is critical for glucokinase interaction (Kamata et al., 2004; Zelent et al., 2011). Additionally, functional studies have shown that G72R results in increased activity compared to wild type, as well as decreased thermal stability of the protein (Sagen et al., 2006; Raimondo et al., 2014). Therefore, we consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000029872 SCV000052527 pathogenic Maturity-onset diabetes of the young, type 2 2011-08-18 criteria provided, single submitter curation Converted during submission to Pathogenic.

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