ClinVar Miner

Submissions for variant NM_000161.3(GCH1):c.626+5G>A

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV003443388 SCV004168332 likely pathogenic not provided 2023-04-24 criteria provided, single submitter clinical testing Reported in a patient with L-dopa responsive dystonia in published literature (Steinberger et al., 2000); Intronic +5 splice site variant in a gene for which loss of function is a known mechanism of disease, and splice predictors support a deleterious effect; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 11113234)
Labcorp Genetics (formerly Invitae), Labcorp RCV003778486 SCV004570945 uncertain significance Dystonia 5; GTP cyclohydrolase I deficiency 2023-07-06 criteria provided, single submitter clinical testing 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. This sequence change falls in intron 5 of the GCH1 gene. It does not directly change the encoded amino acid sequence of the GCH1 protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with dystonia (PMID: 11113234). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site.

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