ClinVar Miner

Submissions for variant NM_000360.4(TH):c.604C>T (p.Arg202Cys)

gnomAD frequency: 0.00001  dbSNP: rs1021029193
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001825549 SCV002213928 likely pathogenic Autosomal recessive DOPA responsive dystonia 2023-03-27 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg233 amino acid residue in TH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9703425, 10407773, 20430833, 20823027, 24753243, 26276013). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TH protein function. ClinVar contains an entry for this variant (Variation ID: 640660). This variant has not been reported in the literature in individuals affected with TH-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 233 of the TH protein (p.Arg233Cys).
Natera, Inc. RCV001825549 SCV002085388 uncertain significance Autosomal recessive DOPA responsive dystonia 2020-10-30 no assertion criteria provided clinical testing
Undiagnosed Diseases Network, NIH RCV001825549 SCV004812026 uncertain significance Autosomal recessive DOPA responsive dystonia 2024-01-29 no assertion criteria provided clinical testing

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