ClinVar Miner

Submissions for variant NM_000161.3(GCH1):c.1A>G (p.Met1Val)

dbSNP: rs1555362907
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Total submissions: 2
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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.
GeneDx 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)

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