Submissions for variant NM_000360.4(TH):c.16G>A (p.Ala6Thr)

gnomAD frequency: 0.00462  dbSNP: rs74555599

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000609157	SCV000291895	benign	Autosomal recessive DOPA responsive dystonia	2025-01-30	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000488317	SCV000574870	likely benign	not provided	2024-11-01	criteria provided, single submitter	clinical testing	TH: BS2
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000609157	SCV000745022	benign	Autosomal recessive DOPA responsive dystonia	2016-02-05	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV001844099	SCV000844486	benign	not specified	2024-08-20	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000609157	SCV001262352	benign	Autosomal recessive DOPA responsive dystonia	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 rule this variant out of causing disease. Therefore, this variant is classified as benign.
GeneDx	RCV000488317	SCV001898138	benign	not provided	2019-07-24	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001844099	SCV002104131	benign	not specified	2022-02-18	criteria provided, single submitter	clinical testing	Variant summary: TH c.16G>A (p.Ala6Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0042 in 246498 control chromosomes in the gnomAD database, including 7 homozygotes. The observed variant frequency is approximately 3.8 fold of the estimated maximal expected allele frequency for a pathogenic variant in TH causing Segawa Syndrome, Autosomal Recessive phenotype (0.0011), strongly suggesting that the variant is benign. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and a predominant consensus as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Breakthrough Genomics, Breakthrough Genomics	RCV000488317	SCV005321310	benign	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000609157	SCV000733021	likely benign	Autosomal recessive DOPA responsive dystonia		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000609157	SCV001457482	benign	Autosomal recessive DOPA responsive dystonia	2020-04-12	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003919990	SCV004731120	benign	TH-related disorder	2020-05-22	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).