Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000030357 | SCV000053024 | likely pathogenic | Familial X-linked hypophosphatemic vitamin D refractory rickets | 2011-08-18 | criteria provided, single submitter | curation | Converted during submission to Likely pathogenic. |
Gene |
RCV000486450 | SCV000570862 | likely pathogenic | not provided | 2016-07-26 | criteria provided, single submitter | clinical testing | The c.349+1 G>C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The 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. While this variant destroys the canonical splice donor site in intron 3, the adjacent exon 3 remains in-frame. In the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
Labcorp Genetics |
RCV000486450 | SCV004509443 | pathogenic | not provided | 2023-01-05 | 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: 36678). Disruption of this splice site has been observed in individuals with hypophosphatemia (PMID: 10737991, 30682568). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 3 of the PHEX gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PHEX are known to be pathogenic (PMID: 9097956, 9106524, 19219621). |