Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute Of Human Genetics Munich, |
RCV000505400 | SCV000599702 | pathogenic | Familial X-linked hypophosphatemic vitamin D refractory rickets | 2017-06-12 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001060115 | SCV001224778 | pathogenic | not provided | 2020-07-10 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change replaces cysteine with arginine at codon 406 of the PHEX protein (p.Cys406Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with X-linked hypophosphatemia (PMID: 24756041, Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 438566). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Cys406 amino acid residue in PHEX. Other variant(s) that disrupt this residue have been observed in individuals with PHEX-related conditions (PMID: 29505567, 23079138, 29460029), which suggests that this may be a clinically significant amino acid residue. |