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

dbSNP: rs1085308012

Total submissions: 3

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 Munich, Klinikum Rechts Der Isar, TU München	RCV000505465	SCV000599621	pathogenic	Familial X-linked hypophosphatemic vitamin D refractory rickets	2013-10-31	criteria provided, single submitter	clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV000488975	SCV002051494	uncertain significance	not provided	2020-11-24	criteria provided, single submitter	clinical testing	PP3, PM5_Supporting, PM2