ClinVar Miner

Submissions for variant NM_000161.3(GCH1):c.344-1G>A (rs1555360050)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000634832 SCV000756176 pathogenic Dystonia 5, Dopa-responsive type; GTP cyclohydrolase I deficiency 2017-10-05 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 1 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). This variant has been reported in individuals affected with dystonia (PMID: 8619546, Invitae). Experimental studies have shown that this acceptor splice site variant leads to skipping of exon 2 and reduced mRNA expresssion (PMID: 8619546). 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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