Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute Of Human Genetics Munich, |
RCV000505438 | SCV000599606 | pathogenic | Familial X-linked hypophosphatemic vitamin D refractory rickets | 2017-06-12 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001307376 | SCV001496786 | pathogenic | not provided | 2022-11-29 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys733 amino acid residue in PHEX. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 22527485, 25839938). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PHEX protein function. ClinVar contains an entry for this variant (Variation ID: 438487). This missense change has been observed in individuals with X-linked hypophosphatemia (XLH) (PMID: 10439971; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 733 of the PHEX protein (p.Cys733Ser). |