Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001851795 | SCV002140963 | pathogenic | not provided | 2021-10-25 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with tyrosine at codon 85 of the PHEX protein (p.Cys85Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Cys85 amino acid residue in PHEX. Other variant(s) that disrupt this residue have been observed in individuals with PHEX-related conditions (PMID: 9199930, 10737991, 30682568), 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: 10817). This variant is also known as Cys82Tyr. This missense change has been observed in individual(s) with hypophosphatemic rickets (PMID: 9106524, 11502829). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (ExAC no frequency). |
| OMIM | RCV000011564 | SCV000031796 | pathogenic | Familial X-linked hypophosphatemic vitamin D refractory rickets | 1997-04-01 | no assertion criteria provided | literature only |