ClinVar Miner

Submissions for variant NM_000444.6(PHEX):c.2104C>T (p.Arg702Ter) (rs886041226)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000315034 SCV000329464 pathogenic not provided 2018-08-14 criteria provided, single submitter clinical testing The R702X nonsense variant in the PHEX gene has been reported previously in association with hypophosphatemic rickets, including an instance of de novo inheritance (Rowe et al., 1997; Zhang et al., 2015). This pathogenic variant is predicted to cause loss of normal protein function through protein truncation. The R702X variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.
Institute of Human Genetics, Klinikum rechts der Isar RCV000505471 SCV000599661 pathogenic Familial X-linked hypophosphatemic vitamin D refractory rickets 2017-06-12 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000315034 SCV001144926 pathogenic not provided 2018-10-04 criteria provided, single submitter clinical testing The variant creates a premature nonsense codon, and is therefore predicted to significantly disrupt the protein structure. Found in at least one symptomatic patient, and not found in general population data.
Invitae RCV000315034 SCV001214302 pathogenic not provided 2019-12-30 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the PHEX gene (p.Arg702*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 48 amino acids of the PHEX protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with hypophosphatemic rickets (PMID: 29505567) and in several individuals with sporadic or familial hypophosphatemic rickets (PMID: 9097956, 23079138, 21902834, 9768674). ClinVar contains an entry for this variant (Variation ID: 279872). For these reasons, this variant has been classified as Pathogenic.

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