ClinVar Miner

Submissions for variant NM_000360.4(TH):c.364C>T (p.Arg122Ter)

gnomAD frequency: 0.00002  dbSNP: rs771610752
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521520 SCV000616894 pathogenic not provided 2018-04-13 criteria provided, single submitter clinical testing The R153X variant in the TH gene has been reported previously in association with autosomal recessive tyrosine hydroxylase deficiency (Mak et al., 2010; Chi et al., 2012). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R153X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret R153X as a pathogenic variant.
Invitae RCV000671827 SCV000947427 pathogenic Autosomal recessive DOPA responsive dystonia 2021-09-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg153*) in the TH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TH are known to be pathogenic (PMID: 22264700, 24753243). This variant is present in population databases (rs771610752, ExAC 0.04%). This premature translational stop signal has been observed in individuals with tyrosine hydroxylase deficiency (PMID: 20056467, 22264700, 28087438). ClinVar contains an entry for this variant (Variation ID: 449110). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.
3billion RCV000671827 SCV002058733 pathogenic Autosomal recessive DOPA responsive dystonia 2022-01-03 criteria provided, single submitter clinical testing Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000059, PM2_M). The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000449110, PMID:20056467). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Counsyl RCV000671827 SCV000796850 pathogenic Autosomal recessive DOPA responsive dystonia 2018-01-02 no assertion criteria provided clinical testing
SingHealth Duke-NUS Institute of Precision Medicine RCV000671827 SCV000853144 likely pathogenic Autosomal recessive DOPA responsive dystonia 2017-06-07 no assertion criteria provided curation
Natera, Inc. RCV000671827 SCV001463820 pathogenic Autosomal recessive DOPA responsive dystonia 2020-09-16 no assertion criteria provided clinical testing

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