Submissions for variant NM_000360.4(TH):c.409C>T (p.Arg137Cys)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003077096	SCV003455457	uncertain significance	Autosomal recessive DOPA responsive dystonia	2024-11-11	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 168 of the TH protein (p.Arg168Cys). This variant is present in population databases (rs548495726, gnomAD 0.006%). This missense change has been observed in individual(s) with Parkinson's disease (PMID: 27185167). ClinVar contains an entry for this variant (Variation ID: 2147253). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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.
GeneDx	RCV004779423	SCV005392364	uncertain significance	not provided	2024-12-30	criteria provided, single submitter	clinical testing	Reported in the heterozygous state without a second TH variant in a patient with Parkinson disease in published literature (PMID: 27185167); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27185167)