ClinVar Miner

Submissions for variant NM_000161.3(GCH1):c.631_632del (p.Met211fs) (rs886039379)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255238 SCV000321711 pathogenic not provided 2016-06-21 criteria provided, single submitter clinical testing The c.631_632delAT variant in the GCH1 gene has been reported previously in multiple individuals with dopa-responsive dystonia (Furukawa et al., 1998; Bandmann et al., 1998; Clot et al., 2009; Sun et al., 2014). The c.631_632delAT variant causes a frameshift starting with codon Methionine 211, changes this amino acid to a Valine residue, and creates a premature Stop codon at position 38 of the new reading frame, denoted p.Met211ValfsX38. This variant is predicted to cause loss of normal protein function through protein truncation. The c.631_632delAT variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.631_632delAT as a pathogenic variant.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001197727 SCV001368506 pathogenic Dystonia 5 2018-10-29 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PVS1,PS1,PM2.
Invitae RCV001221402 SCV001393445 pathogenic Dystonia 5; GTP cyclohydrolase I deficiency 2019-07-08 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the GCH1 gene (p.Met211Valfs*38). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 40 amino acids of the GCH1 protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals and families affected with dopa-responsive dystonia (PMID: 9778264, 19491146, 23430498). ClinVar contains an entry for this variant (Variation ID: 265173). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV001266568 SCV001444744 pathogenic Inborn genetic diseases 2020-03-24 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000255238 SCV001446691 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing

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