Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001068909 | SCV001234044 | likely pathogenic | 6-Pyruvoyl-tetrahydrobiopterin synthase deficiency | 2019-12-23 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Asp136 amino acid residue in PTS. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11388593, 9222757, 25418970). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in combination with another PTS variant in an individual affected with hyperphenylalaninemia (PMID: 11388593). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with glycine at codon 136 of the PTS protein (p.Asp136Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. |