Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV000990544 | SCV001141555 | likely pathogenic | Familial X-linked hypophosphatemic vitamin D refractory rickets | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001858726 | SCV002230714 | pathogenic | not provided | 2021-10-27 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). A different variant (c.2077T>A) giving rise to the same protein effect has been determined to be pathogenic (PMID: 30682568). This suggests that this variant is also likely to be causative of disease. ClinVar contains an entry for this variant (Variation ID: 803773). 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. For these reasons, this variant has been classified as Pathogenic. This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 693 of the PHEX protein (p.Cys693Ser). |