Submissions for variant NM_000444.6(PHEX):c.58C>T (p.Arg20Ter)

dbSNP: rs770573978

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000438600	SCV000516634	pathogenic	not provided	2016-03-04	criteria provided, single submitter	clinical testing	The R20X nonsense variant in the PHEX gene has been frequently reported in association withX-Linked Hypophosphatemic Rickets (Rowe et al., 1997; Francis et al., 1997; Cho et al., 2005). TheR20X variant was not observed in approximately 6,500 individuals of European and African Americanancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant inthese populations. This pathogenic variant is predicted to cause loss of normal protein function eitherthrough protein truncation or nonsense-mediated mRNA decay.
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000505445	SCV000599623	pathogenic	Familial X-linked hypophosphatemic vitamin D refractory rickets	2013-10-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000438600	SCV000963405	pathogenic	not provided	2023-10-22	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg20*) 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 individuals with X-linked hypophosphatemic rickets (PMID: 9097956, 9199930). ClinVar contains an entry for this variant (Variation ID: 379502). For these reasons, this variant has been classified as Pathogenic.
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV000505445	SCV002059964	pathogenic	Familial X-linked hypophosphatemic vitamin D refractory rickets	2022-01-13	criteria provided, single submitter	clinical testing
Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Peking Union Medical College Hospital	RCV000505445	SCV001482393	pathogenic	Familial X-linked hypophosphatemic vitamin D refractory rickets	2019-05-31	no assertion criteria provided	research