ClinVar Miner

Submissions for variant NM_000360.4(TH):c.1348C>T (p.Arg450Cys)

gnomAD frequency: 0.00002  dbSNP: rs375084700
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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 RCV001275013 SCV002237380 uncertain significance Autosomal recessive DOPA responsive dystonia 2021-10-11 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 481 of the TH protein (p.Arg481Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs375084700, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with TH-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). 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.
Ambry Genetics RCV002554439 SCV003755759 uncertain significance Inborn genetic diseases 2021-08-17 criteria provided, single submitter clinical testing The c.1348C>T (p.R450C) alteration is located in exon 13 (coding exon 13) of the TH gene. This alteration results from a C to T substitution at nucleotide position 1348, causing the arginine (R) at amino acid position 450 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001275013 SCV001459703 uncertain significance Autosomal recessive DOPA responsive dystonia 2020-09-16 no assertion criteria provided clinical testing

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