ClinVar Miner

Submissions for variant NM_000161.3(GCH1):c.-22C>T

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003783614 SCV004570783 pathogenic Dystonia 5; GTP cyclohydrolase I deficiency 2023-09-22 criteria provided, single submitter clinical testing This variant occurs in a non-coding region of the GCH1 gene. It does not change the encoded amino acid sequence of the GCH1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with dopa-responsive dystonia (PMID: 10825351, 21674621). It has also been observed to segregate with disease in related individuals. This variant is also known as +142C>T. Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects GCH1 function (PMID: 24124602). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV004801396 SCV005421326 likely pathogenic not provided 2024-05-23 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect as the variant creates an upstream open reading frame that both inhibits translation and generates a 73 amino acid peptide that accumulates in the nucleus (PMID: 28366877); Nucleotide is not conserved across species and the substitution has no predicted effect on splicing; Not observed at significant frequency in large population cohorts (gnomAD); Also known as +142C>T; This variant is associated with the following publications: (PMID: 16917893, 10825351, 19491146, 21674621, SilvaJ2017[Review], 24124602, 28366877)

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