Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000413078 | SCV000490712 | likely pathogenic | not provided | 2018-08-09 | criteria provided, single submitter | clinical testing | The R567P missense variant in the PHEX gene has been reported previously in a sporadic" case ofhypophosphatemic rickets (Tyynismaa et al., 2000). The R567P variant was not observed inapproximately 6,500 individuals of European and African American ancestry in the NHLBI ExomeSequencing Project, indicating it is not a common benign variant in these populations. The R567Pvariant is a non-conservative amino acid substitution, which is likely to impact secondary proteinstructure as these residues differ in polarity, charge, size and/or other properties. This substitutionoccurs at a position that is conserved across species and in silico analysis predicts this variant isprobably damaging to the protein structure/function. The R567P variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded." |
Invitae | RCV000413078 | SCV001556674 | pathogenic | not provided | 2022-02-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 372459). This missense change has been observed in individuals with hypophosphatemic rickets (PMID: 10737991; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 567 of the PHEX protein (p.Arg567Pro). This variant also falls at the last nucleotide of exon 16, which is part of the consensus splice site for this exon. |