ClinVar Miner

Submissions for variant NM_003560.4(PLA2G6):c.673C>T (p.His225Tyr) (rs587784359)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000147331 SCV000194704 likely pathogenic Iron accumulation in brain 2013-02-08 criteria provided, single submitter clinical testing
GeneDx RCV000484666 SCV000567163 pathogenic not provided 2015-08-10 criteria provided, single submitter clinical testing The H225Y variant in the PLA2G6 gene has been reported previously in homozygous state in 4 affectedindividuals from a single kindred who presented with progressive childhood ataxia, slow cognitive decline,psychiatric symptoms, optic nerve pallor with upward gaze palsy, cerebellar atrophy, and loss of ambulationin the late teenage years (Salih et al., 2013; Khan et al., 2014). The H225Y substitution was not observed inapproximately 6500 individuals of European and African American ancestry in the NHLBI ExomeSequencing Project, indicating it is not a common benign variant in these populations. The H225Y variantis a non-conservative amino acid substitution, which is likely to impact secondary protein structure as theseresidues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that isconserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variantis damaging to the protein structure/function. We interpret H225Y as a pathogenic variant.

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