ClinVar Miner

Submissions for variant NM_000161.3(GCH1):c.506C>G (p.Ala169Gly)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003086282 SCV003473058 uncertain significance Dystonia 5; GTP cyclohydrolase I deficiency 2022-09-13 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 169 of the GCH1 protein (p.Ala169Gly). This variant is not present in population databases (gnomAD no frequency). 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.
GeneDx RCV003332407 SCV004040197 uncertain significance not provided 2023-03-26 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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