Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000990532 | SCV001141542 | likely pathogenic | Familial X-linked hypophosphatemic vitamin D refractory rickets | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003688891 | SCV004452171 | likely pathogenic | not provided | 2023-04-05 | criteria provided, single submitter | clinical testing | This variant disrupts the p.Ala573 amino acid residue in PHEX. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10439971; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 573 of the PHEX protein (p.Ala573Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of hypophosphatemia (Invitae). ClinVar contains an entry for this variant (Variation ID: 803763). 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. |