ClinVar Miner

Submissions for variant NM_000444.6(PHEX):c.871C>T (p.Arg291Ter) (rs866429868)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000412793 SCV000490706 pathogenic not provided 2018-05-15 criteria provided, single submitter clinical testing The R291X nonsense variant in the PHEX gene (also referred to as R288X using an alternate reference sequence) has been reported previously in association with X-linked hypophosphatemic rickets (Holm et al., 1997; Sato et al., 2000; Sheng et al., 2015; Li et al., 2016). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Additionally, the R291X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Therefore, we interpret the R291X variant to be pathogenic.
Institute of Human Genetics,Klinikum rechts der Isar RCV000505415 SCV000599608 pathogenic Familial X-linked hypophosphatemic vitamin D refractory rickets 2015-04-17 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000505415 SCV000893826 pathogenic Familial X-linked hypophosphatemic vitamin D refractory rickets 2018-10-31 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000412793 SCV001144931 pathogenic not provided 2019-07-10 criteria provided, single submitter clinical testing The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data.
Invitae RCV000412793 SCV001225097 pathogenic not provided 2019-11-15 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg291*) 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 to segregate with hypophosphatemic rickets in a family (PMID: 11004247) and it has also been observed in unrelated individuals affected with this condition (PMID: 9106524, 30298486, 26040324, 23466123, 29460029). ClinVar contains an entry for this variant (Variation ID: 372454). 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.

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