Submissions for variant NM_000161.3(GCH1):c.68C>T (p.Pro23Leu)

gnomAD frequency: 0.00389  dbSNP: rs41298432

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000263675	SCV000387124	benign	GTP cyclohydrolase I deficiency	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000430107	SCV000510805	likely benign	not provided	2016-08-04	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000455719	SCV000539228	likely benign	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in 1 individual with dystonia in trans with a nonsense variant (Jarman 1997). In a family with 2 members, it was identified in 2 affected individuals with DOPA-responsive dystonia and 1 with Parkinsons, this variant was identified in 1 individual with dystonia and 1 with Parkinsons (who also had a Phe104Leu variant) (Mencacci 2014). One of the family members with dystonia only had the Phe104Leu variant. This variant was described as benign due to its MAF. MAF 1.5% in Eur chr.
CeGaT Center for Human Genetics Tuebingen	RCV000430107	SCV000608703	likely benign	not provided	2024-08-01	criteria provided, single submitter	clinical testing	GCH1: BS2
Labcorp Genetics (formerly Invitae), Labcorp	RCV001084264	SCV000631822	benign	Dystonia 5; GTP cyclohydrolase I deficiency	2024-01-31	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000430107	SCV000842148	benign	not provided	2017-09-29	criteria provided, single submitter	clinical testing
Mendelics	RCV000263675	SCV001139463	benign	GTP cyclohydrolase I deficiency	2019-05-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001111087	SCV001268594	benign	Dystonia 5	2018-03-06	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Elsea Laboratory, Baylor College of Medicine	RCV001084264	SCV001424236	uncertain significance	Dystonia 5; GTP cyclohydrolase I deficiency	2020-04-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000430107	SCV001872141	benign	not provided	2018-12-04	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 31213404, 30314816, 25497597, 9328244, 19332422, 24993959)
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000430107	SCV001739888	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000430107	SCV001800529	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000430107	SCV001922547	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003940216	SCV004748440	likely benign	GCH1-related disorder	2020-10-06	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).