ClinVar Miner

Submissions for variant NM_000161.3(GCH1):c.11G>A (p.Gly4Asp)

dbSNP: rs2140127797
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001806483 SCV002050365 uncertain significance not provided 2021-06-29 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533)
Labcorp Genetics (formerly Invitae), Labcorp RCV003772219 SCV004587195 uncertain significance Dystonia 5; GTP cyclohydrolase I deficiency 2023-01-09 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with GCH1-related conditions. 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. 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. ClinVar contains an entry for this variant (Variation ID: 1331138). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 4 of the GCH1 protein (p.Gly4Asp).

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