ClinVar Miner

Submissions for variant NM_000360.4(TH):c.1301C>G (p.Ser434Cys)

gnomAD frequency: 0.00001  dbSNP: rs767211543
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670046 SCV000794857 uncertain significance Autosomal recessive DOPA responsive dystonia 2017-10-18 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000670046 SCV000963424 uncertain significance Autosomal recessive DOPA responsive dystonia 2022-06-22 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 465 of the TH protein (p.Ser465Cys). This variant is present in population databases (rs767211543, gnomAD 0.004%). This missense change has been observed in individual(s) with dystonia (PMID: 28186668). ClinVar contains an entry for this variant (Variation ID: 554418). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts the p.Ser465 amino acid residue in TH. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 33233562). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. RCV000670046 SCV002091012 uncertain significance Autosomal recessive DOPA responsive dystonia 2021-02-22 no assertion criteria provided clinical testing

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