ClinVar Miner

Submissions for variant NM_000161.3(GCH1):c.206C>T (p.Pro69Leu) (rs56127440)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000362082 SCV000387120 likely benign Dystonia 5 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV000265088 SCV000387121 likely benign GTP cyclohydrolase I deficiency 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000585377 SCV000692790 likely benign not provided 2019-04-01 criteria provided, single submitter clinical testing
Invitae RCV000687434 SCV000814999 uncertain significance Dystonia 5; GTP cyclohydrolase I deficiency 2020-10-27 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 69 of the GCH1 protein (p.Pro69Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs56127440, ExAC 0.06%). This variant has been reported in individuals affected with dystonia, parkinsonism, hereditary spastic paraplegia, as well as in unaffected control individuals (PMID: 15389992, 27217339, 19491146, 25398234, 30314816, 25125585, 27185167, 26230973). ClinVar contains an entry for this variant (Variation ID: 161247). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Mendelics RCV000265088 SCV001139462 benign GTP cyclohydrolase I deficiency 2019-05-28 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000585377 SCV001143995 uncertain significance not provided 2018-12-14 criteria provided, single submitter clinical testing
CSER _CC_NCGL, University of Washington RCV000148505 SCV000190216 likely benign Hyperphenylalaninemia due to tetrahydrobiopterin deficiency 2014-06-01 no assertion criteria provided research

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