ClinVar Miner

Submissions for variant NM_000161.3(GCH1):c.279G>T (p.Lys93Asn)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002782690 SCV003590011 uncertain significance Inborn genetic diseases 2021-10-26 criteria provided, single submitter clinical testing The c.279G>T (p.K93N) alteration is located in exon 1 (coding exon 1) of the GCH1 gene. This alteration results from a G to T substitution at nucleotide position 279, causing the lysine (K) at amino acid position 93 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003777749 SCV004573663 uncertain significance Dystonia 5; GTP cyclohydrolase I deficiency 2023-09-27 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 93 of the GCH1 protein (p.Lys93Asn). 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. ClinVar contains an entry for this variant (Variation ID: 2257143). 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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