ClinVar Miner

Submissions for variant NM_000161.3(GCH1):c.571G>A (p.Val191Ile)

gnomAD frequency: 0.00001  dbSNP: rs762208304
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centogene AG - the Rare Disease Company RCV001809073 SCV002059439 uncertain significance Dystonia 5 2020-04-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001869592 SCV002298571 uncertain significance Dystonia 5; GTP cyclohydrolase I deficiency 2022-08-23 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 191 of the GCH1 protein (p.Val191Ile). This variant is present in population databases (rs762208304, gnomAD 0.002%). This missense change has been observed in individual(s) with dopa-responsive dystonia (PMID: 9778264). ClinVar contains an entry for this variant (Variation ID: 1333858). 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.

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