ClinVar Miner

Submissions for variant NM_000209.3(PDX1):c.52T>C (p.Cys18Arg) (rs137852785)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000439286 SCV000521051 likely pathogenic not provided 2016-10-10 criteria provided, single submitter clinical testing The C18R variant in the PDX1 gene has been reported previously in association with diabetes (Macfarlane et al., 1999; Flannick et al., 2013); however, the variant has been observed in unaffected family members by Macfarlane et al., and in a control subject in another study (Macfarlane et al., 1999; Edghill et al., 2011). The variant was not observed at any significant frequency in approximately 5,600 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. G18R variant 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 that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, functional studies have shown that G18R results in a moderate reduction in insulin gene activation by the PDX1 protein (Macfarlane et al., 1999). Therefore, this variant is likely pathogenic.
OMIM RCV000009412 SCV000029630 risk factor Diabetes mellitus type 2 1999-11-01 no assertion criteria provided literature only

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