ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.1340G>A (p.Arg447Gln) (rs1131691416)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000494422 SCV000582084 likely pathogenic not provided 2017-05-11 criteria provided, single submitter clinical testing The R447Q variant has been published previously in association with MODY (Pruhova et al., 2010; Esquiaveto-Aun et al., 2015; de Santana et al., 2017). The variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). R447Q is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position where amino acids with similar properties to Arginine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Missense variants in the same codon (R447P/G) and in nearby residues (S445C, G446R, G448V, A449T/S, A450T/V/D) have been reported in the Human Gene Mutation Database in association with MODY (Stenson et al., 2014), supporting the functional importance of this region of the protein. In summary, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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