ClinVar Miner

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

dbSNP: rs137853271
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Total submissions: 10
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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 Munich, Klinikum Rechts Der Isar, TU München RCV000011569 SCV000599613 pathogenic Familial X-linked hypophosphatemic vitamin D refractory rickets 2015-04-17 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000414471 SCV001222252 pathogenic not provided 2023-11-07 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. Loss-of-function variants in PHEX are known to be pathogenic (PMID: 9097956, 9106524, 19219621). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with X-linked hypophosphatemia (PMID: 16303832, 22261628; Invitae). ClinVar contains an entry for this variant (Variation ID: 10822). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics 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].
Genetics and Molecular Pathology, SA Pathology RCV000011569 SCV004175573 pathogenic Familial X-linked hypophosphatemic vitamin D refractory rickets 2023-06-26 criteria provided, single submitter clinical testing The PHEX c.1699C>T variant is classified as Pathogenic (PVS1, PS4_Moderate, PS3_Moderate, PM2, PP1_Supporting). The PHEX c.1699C>T variant is a single nucleotide change which is predicted to result in premature termination of the protein product at codon 567 (PVS1). This variant has been previously reported in multiple individuals with X-linked hypophosphatemia in the literature (PMID: 29901142, PMID: 22101457, PMID: 18162710), including a patient who was found to be mosaic for this variant (PMID: 16303832) (PS4_Moderate). Functional studies have shown this variant causes a trafficking defect resulting in intracellular retention of PHEX protein in transfected cells (PMID: 32329911) (PS3_moderate). This variant is absent from population databases (PM2). This variant was found to co-segregate with disease in two unrelated families (PP1_supporting). The variant has been reported in dbSNP (rs137853271) and has been reported as Pathogenic by other diagnostic laboratories (ClinVar Variation ID: 10822). It has been reported in HGMD (CM060430).
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV000011569 SCV004231764 pathogenic Familial X-linked hypophosphatemic vitamin D refractory rickets 2024-01-12 criteria provided, single submitter clinical testing
OMIM RCV000011569 SCV000031801 pathogenic Familial X-linked hypophosphatemic vitamin D refractory rickets 2006-02-01 no assertion criteria provided literature only
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000414471 SCV001951780 pathogenic not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000414471 SCV001968990 pathogenic not provided no assertion criteria provided clinical testing

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