ClinVar Miner

Submissions for variant NM_000161.3(GCH1):c.22G>A (p.Ala8Thr)

gnomAD frequency: 0.00001  dbSNP: rs529381971
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000711751 SCV000842144 uncertain significance not provided 2018-07-09 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001055986 SCV001220403 uncertain significance Dystonia 5; GTP cyclohydrolase I deficiency 2022-10-30 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 8 of the GCH1 protein (p.Ala8Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with GCH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 585905). 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.
Ambry Genetics RCV004026811 SCV004873346 uncertain significance Inborn genetic diseases 2023-12-20 criteria provided, single submitter clinical testing The c.22G>A (p.A8T) alteration is located in exon 1 (coding exon 1) of the GCH1 gene. This alteration results from a G to A substitution at nucleotide position 22, causing the alanine (A) at amino acid position 8 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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