Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000556657 | SCV000631818 | uncertain significance | Dystonia 5; GTP cyclohydrolase I deficiency | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces proline with arginine at codon 40 of the GCH1 protein (p.Pro40Arg). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and arginine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with GCH1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Ambry Genetics | RCV002527705 | SCV003652463 | uncertain significance | Inborn genetic diseases | 2022-10-26 | criteria provided, single submitter | clinical testing | The c.119C>G (p.P40R) alteration is located in exon 1 (coding exon 1) of the GCH1 gene. This alteration results from a C to G substitution at nucleotide position 119, causing the proline (P) at amino acid position 40 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |