Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000444535 | SCV000524592 | likely pathogenic | not provided | 2016-03-03 | criteria provided, single submitter | clinical testing | The H580R variant in the PHEX gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. However, a missense variant at this same codon (H580P) as well as missense variants in neighboring codons (G579R, G579V, and H584P) have been reported in the Human Gene Mutation Database in association with hypophosphatemic rickets (Stenson et al., 2014), supporting the functional importance of this region of the protein. The H580R variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The H580R variant is a conservative amino acid substitution, which occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. The H580R variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678304 | SCV000804363 | likely pathogenic | Familial X-linked hypophosphatemic vitamin D refractory rickets | 2018-02-23 | criteria provided, single submitter | provider interpretation | This variant was identified in a 5 year old female with a genetic and biochemical diagnosis of Sanfilippo syndrome. The variant is absent from the gnomAD database, and it was found to be de novo (with maternity and paternity confirmed). Computational models predict it to be deleterious. Other missense variants involving this codon (H580P) and nearby codons have been reported in the Human Gene Mutation Database. |