ClinVar Miner

Submissions for variant NM_000161.3(GCH1):c.509+1_509+3delinsTGTGAG (rs1594982939)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000794588 SCV000934006 pathogenic Dystonia 5; GTP cyclohydrolase I deficiency 2019-01-07 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 3 of the GCH1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). Variants that affect this splice site have been observed in several individuals affected with dopa-responsive dystonia (PMID:  11113234, 14509676). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in GCH1 are known to be pathogenic (PMID: 19491146). For these reasons, this variant has been classified as Pathogenic.

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