Submissions for variant NM_000444.6(PHEX):c.1645C>T (p.Arg549Ter)

dbSNP: rs886041224

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000280838	SCV000329461	pathogenic	not provided	2019-05-15	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 16636593, 24836714, 21902834, 19219621, 24926462, 26051471, 29505567, 14564077, 14564066, 23079138, 9097956, 29460029, 30682568, 31102713)
Athena Diagnostics	RCV000280838	SCV000614442	pathogenic	not provided	2017-05-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000280838	SCV001237314	pathogenic	not provided	2024-01-13	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg549*) 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 hypophosphatemia (PMID: 9097956, 24836714, 29460029). ClinVar contains an entry for this variant (Variation ID: 279870). For these reasons, this variant has been classified as Pathogenic.
3billion	RCV002250611	SCV002521064	pathogenic	Familial X-linked hypophosphatemic vitamin D refractory rickets	2022-05-22	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000279870 / PMID: 9097956). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
MGZ Medical Genetics Center	RCV002250611	SCV002580948	pathogenic	Familial X-linked hypophosphatemic vitamin D refractory rickets	2022-07-19	criteria provided, single submitter	clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV002250611	SCV004013240	pathogenic	Familial X-linked hypophosphatemic vitamin D refractory rickets	2023-05-23	criteria provided, single submitter	clinical testing	PVS1, PS4
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV002250611	SCV004231765	pathogenic	Familial X-linked hypophosphatemic vitamin D refractory rickets	2024-01-12	criteria provided, single submitter	clinical testing