Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000673779 | SCV000799022 | likely pathogenic | Autosomal recessive DOPA responsive dystonia | 2018-04-04 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000673779 | SCV001381768 | pathogenic | Autosomal recessive DOPA responsive dystonia | 2023-11-08 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu99Argfs*15) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with TH deficiency (PMID: 11160968, 12891655). ClinVar contains an entry for this variant (Variation ID: 557613). For these reasons, this variant has been classified as Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000673779 | SCV003928745 | likely pathogenic | Autosomal recessive DOPA responsive dystonia | 2023-04-12 | criteria provided, single submitter | clinical testing | Variant summary: TH c.296delT (p.Leu99ArgfsX15) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 245908 control chromosomes (gnomAD). c.296delT has been reported in the literature in at least one compound heterozygous individual affected with Segawa Syndrome, Autosomal Recessive (Furukawa_2001). The variant was also found occuring in a heterozygous adult with late-onset Dopa-responsive Dystonia (Bally_2020). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters have assessed the variant since 2014: one classified the variant as likely pathogenic and two as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV000673779 | SCV004203851 | pathogenic | Autosomal recessive DOPA responsive dystonia | 2023-09-05 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000673779 | SCV002089660 | pathogenic | Autosomal recessive DOPA responsive dystonia | 2020-12-01 | no assertion criteria provided | clinical testing |