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

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000634835	SCV000756179	pathogenic	Dystonia 5; GTP cyclohydrolase I deficiency	2019-05-06	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.
CeGaT Praxis fuer Humangenetik Tuebingen	RCV001090536	SCV001246141	pathogenic	not provided	2018-02-01	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001090536	SCV001447630	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing