Submissions for variant NM_000444.6(PHEX):c.1586_1586+1del

dbSNP: rs886041362

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000369200	SCV000329877	pathogenic	not provided	2021-01-08	criteria provided, single submitter	clinical testing	Canonical splice site variant predicted to result in a null allele 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: 19429806, 30682568, 27840894, 19219621)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000369200	SCV001410567	pathogenic	not provided	2022-05-08	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 280075). This variant is also known as c.1586_1586+1del. This variant has been observed in individuals with hypophosphatemic ricket (PMID: 19219621). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (Splice site) 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).
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV002265718	SCV002059962	pathogenic	Familial X-linked hypophosphatemic vitamin D refractory rickets	2022-01-13	criteria provided, single submitter	clinical testing