ClinVar Miner

Submissions for variant NM_002693.2(POLG):c.694C>T (p.Arg232Cys) (rs770115219)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000433583 SCV000517226 pathogenic not provided 2015-05-18 criteria provided, single submitter clinical testing The R232C variant in the POLG gene has not been reported previously as a pathogenic variantnor as a benign polymorphism, to our knowledge. The R232C substitution was not observed in approximately6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project,indicating it is not a common benign variant in these populations. The R232C variant is a non-conservativeamino acid substitution, which is likely to impact secondary protein structure as these residues differ inpolarity, charge, size and/or other properties. This substitution occurs at a position in the exonucleasedomain that is conserved across species. In silico analysis predicts this variant is probably damaging tothe protein structure/function. Missense variants in the same residue and nearby residues (C224Y,R227W/P, R232G/H) have been reported in the Human Gene Mutation Database in association withPOLG-related disorders (Stenson et al., 2014), supporting the functional importance of this region of theprotein. We interpret R232C as a pathogenic variant.

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