ClinVar Miner

Submissions for variant NM_000444.6(PHEX):c.2078G>A (p.Cys693Tyr) (rs1556200989)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, Klinikum rechts der Isar RCV000505399 SCV000599642 pathogenic Familial X-linked hypophosphatemic vitamin D refractory rickets 2013-10-31 criteria provided, single submitter clinical testing
Invitae RCV001064981 SCV001229919 pathogenic not provided 2019-12-07 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 693 of the PHEX protein (p.Cys693Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with hypophosphatemic rickets (PMID: 10737991, 30682568, Invitae). ClinVar contains an entry for this variant (Variation ID: 438513). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Cys693 amino acid residue in PHEX. Other variant(s) that disrupt this residue have been observed in individuals with PHEX-related conditions (PMID: 30682568, 23079138), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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