ClinVar Miner

Submissions for variant NM_000444.6(PHEX):c.254G>C (p.Cys85Ser)

dbSNP: rs137853269
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000990506 SCV001141510 likely pathogenic Familial X-linked hypophosphatemic vitamin D refractory rickets 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV001869364 SCV002118695 pathogenic not provided 2023-12-06 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 85 of the PHEX protein (p.Cys85Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with X-linked hypophosphatemia (PMID: 30682568). ClinVar contains an entry for this variant (Variation ID: 803739). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PHEX protein function with a positive predictive value of 95%. This variant disrupts the p.Cys85 amino acid residue in PHEX. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9106524, 11502829). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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