Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000796195 | SCV000935699 | pathogenic | Dystonia 5; GTP cyclohydrolase I deficiency | 2024-01-14 | criteria provided, single submitter | clinical testing | This sequence change affects the initiator methionine of the GCH1 mRNA. The next in-frame methionine is located at codon 102. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individuals with dopamine-responsive dystonia (PMID: 9576537, 17557242, 20437540, 21935284, 22373569; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 642685). For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV002245673 | SCV002512911 | pathogenic | not provided | 2022-03-29 | criteria provided, single submitter | clinical testing | Reported in the heterozygous state in a family, including two siblings with dopa-responsive dystonia, their unaffected father, and an unaffected child of one of the siblings, in the published literature (Naiya et al., 2012); Initiation codon variant in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 22373569) |