ClinVar Miner

Submissions for variant NM_000444.6(PHEX):c.1979G>A (p.Trp660Ter) (rs886041369)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000285863 SCV000329884 pathogenic not provided 2018-10-26 criteria provided, single submitter clinical testing The W660X nonsense variant in the PHEX gene has been reported previously in association with X-linked hypophosphatemic rickets (Francis et al., 1997). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The 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. Therefore, we consider this variant to be pathogenic.
Institute of Human Genetics, Klinikum rechts der Isar RCV000505395 SCV000599622 pathogenic Familial X-linked hypophosphatemic vitamin D refractory rickets 2017-06-12 criteria provided, single submitter clinical testing
Invitae RCV000285863 SCV001202041 pathogenic not provided 2019-12-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp660*) 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 hypophosphatemic rickets (PMID: 9199930). ClinVar contains an entry for this variant (Variation ID: 280082). 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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