ClinVar Miner

Submissions for variant NM_000444.6(PHEX):c.1366T>C (p.Trp456Arg) (rs1085308012)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000488975 SCV000577828 likely pathogenic not provided 2015-04-19 criteria provided, single submitter clinical testing The W456R variant has not been published as a pathogenic variant, nor has it been reported as a benign polymorphism to our knowledge. The W456R variant was not observed in approximately 6,500 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 W456R 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. A missense variant at the same residue (W456C) and in a nearby residue (L450P) have been reported in the Human Gene Mutation Database in association with hypophosphatemic rickets (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded.
Institute of Human Genetics, Klinikum rechts der Isar RCV000505465 SCV000599621 pathogenic Familial X-linked hypophosphatemic vitamin D refractory rickets 2013-10-31 criteria provided, single submitter clinical testing

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