ClinVar Miner

Submissions for variant NM_000360.4(TH):c.1361C>A (p.Pro454His)

gnomAD frequency: 0.00001  dbSNP: rs776457245
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489320 SCV000577424 uncertain significance not provided 2024-09-24 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001834591 SCV002113946 uncertain significance Autosomal recessive DOPA responsive dystonia 2022-09-27 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 485 of the TH protein (p.Pro485His). This variant is present in population databases (rs776457245, gnomAD 0.01%). 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: 426863). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
Natera, Inc. RCV001834591 SCV002090314 uncertain significance Autosomal recessive DOPA responsive dystonia 2019-11-11 no assertion criteria provided clinical testing

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