Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Human Genetics Munich, |
RCV000505477 | SCV000599693 | pathogenic | Familial X-linked hypophosphatemic vitamin D refractory rickets | 2013-11-06 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000505477 | SCV002518822 | pathogenic | Familial X-linked hypophosphatemic vitamin D refractory rickets | 2022-05-04 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002524419 | SCV003350412 | uncertain significance | not provided | 2022-08-20 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the p.Leu569 amino acid residue in PHEX. Other variant(s) that disrupt this residue have been observed in individuals with PHEX-related conditions (PMID: 33639975), which suggests that this may be a clinically significant amino acid residue. 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: 438557). This missense change has been observed in individual(s) with clinical features of hypophosphatemic rickets (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 569 of the PHEX protein (p.Leu569Pro). |