Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute Of Human Genetics Munich, |
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 | 2023-07-22 | criteria provided, single submitter | clinical testing | 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: 438513). This missense change has been observed in individuals with hypophosphatemic rickets (PMID: 10737991, 30682568; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 693 of the PHEX protein (p.Cys693Tyr). For these reasons, this variant has been classified as Pathogenic. 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: 23079138, 30682568), which suggests that this may be a clinically significant amino acid residue. |