Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000521636 | SCV000618138 | likely pathogenic | not provided | 2017-10-24 | criteria provided, single submitter | clinical testing | The Y634C has been published as a variant identified in a patient belonging to a cohort diagnosed with a non-specific skeletal dysplasia (Bae et al., 2015). The variant has also been observed at GeneDx to occur apparently de novo in an affected patient. The variant is not observed in large population cohorts (Lek et al., 2016). The Y346C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. A missense variant in this residue (Y346D) has been reported in the Human Gene Mutation Database in association with hypophosphatemic rickets (Stenson et al., 2014). In summary, we consider this variant to be likely pathogenic. |
| Mendelics | RCV000990519 | SCV001141525 | likely pathogenic | Familial X-linked hypophosphatemic vitamin D refractory rickets | 2019-05-28 | criteria provided, single submitter | clinical testing |