Submissions for variant NM_000444.6(PHEX):c.2198G>A (p.Cys733Tyr)

dbSNP: rs1057517981

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000413547	SCV000491266	likely pathogenic	not provided	2016-06-28	criteria provided, single submitter	clinical testing	The C733Y variant has been published previously in association with hypophosphatemic rickets (Jap et al., 2011; Huang et al., 2015). The 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. C733Y 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. Missense variants in the same residue (C733R/S) and in a nearby residue (F731S/Y) 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 likely pathogenic.
CeGaT Center for Human Genetics Tuebingen	RCV000413547	SCV001249134	pathogenic	not provided	2019-11-01	criteria provided, single submitter	clinical testing