Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001231564 | SCV001404091 | pathogenic | Dystonia 5; GTP cyclohydrolase I deficiency | 2019-11-08 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in GCH1 are known to be pathogenic (PMID: 19491146). This variant has been observed in individual(s) with clinical features of GCH1-related dystonia (PMID: 20187889). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu84*) in the GCH1 gene. It is expected to result in an absent or disrupted protein product. |
3billion | RCV002250735 | SCV002521279 | pathogenic | Dystonia 5 | 2022-05-22 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be associated with GCH1 related disorder (ClinVar ID: VCV000958404 / PMID: 20187889 / 3billion dataset). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |