ClinVar Miner

Submissions for variant NM_000444.6(PHEX):c.1699C>T (p.Arg567Ter) (rs137853271)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414471 SCV000490711 pathogenic not provided 2018-08-21 criteria provided, single submitter clinical testing The R567X pathogenic variant in the PHEX gene has been reported previously in association with hypophosphatemic rickets (Goji et al., 2006). It was also identified in one patient from a study of patients with PHEX variants that were diagnosed with hypophosphatemic rickets (vitamin D-resistant rickets, VDRR) (Lee et al., 2012). The R567X 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. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, we interpret R567X in PHEX as a pathogenic variant.
Institute of Human Genetics, Klinikum rechts der Isar RCV000011569 SCV000599613 pathogenic Familial X-linked hypophosphatemic vitamin D refractory rickets 2015-04-17 criteria provided, single submitter clinical testing
Invitae RCV000414471 SCV001222252 pathogenic not provided 2019-11-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg567*) in the PHEX gene. It is expected to result in an absent or disrupted protein product. 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: 16303832, 22261628, Invitae). ClinVar contains an entry for this variant (Variation ID: 10822). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in PHEX are known to be pathogenic (PMID: 9097956, 9106524, 19219621). For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000414471 SCV001249131 pathogenic not provided 2019-10-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV000011569 SCV001523235 pathogenic Familial X-linked hypophosphatemic vitamin D refractory rickets 2020-06-10 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
OMIM RCV000011569 SCV000031801 pathogenic Familial X-linked hypophosphatemic vitamin D refractory rickets 2006-02-01 no assertion criteria provided literature only

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