ClinVar Miner

Submissions for variant NM_000161.3(GCH1):c.458A>G (p.His153Arg)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003783612 SCV004570888 uncertain significance Dystonia 5; GTP cyclohydrolase I deficiency 2023-02-20 criteria provided, single submitter clinical testing This missense change has been observed in individuals with clinical features of dystonia and related disorders (PMID: 19491146; Invitae). 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. This variant disrupts the p.His153 amino acid residue in GCH1. Other variant(s) that disrupt this residue have been observed in individuals with GCH1-related conditions (PMID: 8852666, 19491146, 34997870), which suggests that this may be a clinically significant amino acid residue. 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. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 153 of the GCH1 protein (p.His153Arg).

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