ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.1099G>A (p.Val367Met) (rs1057521092)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000440624 SCV000521045 likely pathogenic not provided 2016-04-11 criteria provided, single submitter clinical testing The V367M variant in the GCK gene has been published previously in association with MODY (Velho et al., 1997). However, familial segregation data was not provided. The variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. V367M is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Functional studies have shown that while V367M does not affect the GCK protein's metabolic response to glucose, it causes conformational changes and negatively affects the posttranscriptional regulation of the protein. (Ding et al., 2010; Markwardt et al., 2012) Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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