ClinVar Miner

Submissions for variant NM_000360.4(TH):c.91-868C>T

gnomAD frequency: 0.00012  dbSNP: rs148235227
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001195971 SCV000814585 uncertain significance Autosomal recessive DOPA responsive dystonia 2022-08-31 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 45 of the TH protein (p.Pro45Leu). This variant is present in population databases (rs148235227, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with TH-related conditions. ClinVar contains an entry for this variant (Variation ID: 567057). 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) performed at Invitae indicates that this missense variant is not expected to disrupt TH protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Centre for Mendelian Genomics, University Medical Centre Ljubljana RCV001195971 SCV001366398 uncertain significance Autosomal recessive DOPA responsive dystonia 2019-01-28 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: No criteria apply.
Ambry Genetics RCV002547110 SCV003599309 likely benign Inborn genetic diseases 2022-01-26 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Natera, Inc. RCV001195971 SCV002089738 uncertain significance Autosomal recessive DOPA responsive dystonia 2019-11-11 no assertion criteria provided clinical testing

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