ClinVar Miner

Submissions for variant NM_000444.6(PHEX):c.1936G>C (p.Asp646His) (rs1556148532)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, Klinikum rechts der Isar RCV000505472 SCV000599638 pathogenic Familial X-linked hypophosphatemic vitamin D refractory rickets 2013-10-31 criteria provided, single submitter clinical testing
Invitae RCV001207802 SCV001379169 likely pathogenic not provided 2020-08-04 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with histidine at codon 646 of the PHEX protein (p.Asp646His). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individuals with hypophosphatemia (Invitae). ClinVar contains an entry for this variant (Variation ID: 438510). 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.Asp646 amino acid residue in PHEX. Other variant(s) that disrupt this residue have been observed in individuals with PHEX-related conditions (PMID: 21050253, Invitae), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.