ClinVar Miner

Submissions for variant NM_000161.3(GCH1):c.626+1G>A (rs1555358507)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000634835 SCV000756179 pathogenic Dystonia 5, Dopa-responsive type; GTP cyclohydrolase I deficiency 2017-11-14 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in the last intron (intron 5) of the GCH1 gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a 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: 9749603, 17101830, 19491146). Nucleotide substitutions within 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, and experimental evidence has shown that this intronic change results in aberrant splicing of exon 5 of the GCH1 mRNA (PMID: 9749603). For these reasons, this variant has been classified as Pathogenic.

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