Submissions for variant NM_000161.3(GCH1):c.89C>G (p.Pro30Arg)

gnomAD frequency: 0.00002  dbSNP: rs1477733062

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001904708	SCV002127016	uncertain significance	Dystonia 5; GTP cyclohydrolase I deficiency	2021-09-01	criteria provided, single submitter	clinical testing	This sequence change replaces proline with arginine at codon 30 of the GCH1 protein (p.Pro30Arg). 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. 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 not expected to disrupt GCH1 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.