ClinVar Miner

Submissions for variant NM_003560.4(PLA2G6):c.2246G>C (p.Trp749Ser) (rs587784351)

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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 RCV000147318 SCV000194691 likely pathogenic Iron accumulation in brain 2013-02-08 criteria provided, single submitter clinical testing
GeneDx RCV000489829 SCV000577841 likely pathogenic not provided 2015-04-10 criteria provided, single submitter clinical testing The W749S variant in the PLA2G6 gene has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The W749S variant was not observed in approximately 6,350 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 W749S 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. In silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, numerous missense variants in nearby residues (R741Q; R741W; R745W; R745P; R747W; E751K; G754V) have been reported in the Human Gene Mutation Database in association with PLA2G6-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. The W749S variant is a strong candidate for a disease-causing variant however, the possibility it may be a rare benign variant cannot be excluded

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