Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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, |
RCV000011569 | SCV000599613 | pathogenic | Familial X-linked hypophosphatemic vitamin D refractory rickets | 2015-04-17 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
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. |
Ce |
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, |
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, |
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, |
RCV000414471 | SCV001951780 | pathogenic | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000414471 | SCV001968990 | pathogenic | not provided | no assertion criteria provided | clinical testing |