ClinVar Miner

Submissions for variant NM_000360.4(TH):c.517C>A (p.Leu173Met)

gnomAD frequency: 0.00001  dbSNP: rs1468608879
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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 RCV001830487 SCV002164570 uncertain significance Autosomal recessive DOPA responsive dystonia 2022-10-13 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 204 of the TH protein (p.Leu204Met). This variant is present in population databases (no rsID available, gnomAD 0.006%), including at least one homozygous and/or hemizygous individual. 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: 566840). 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) has been performed at Invitae 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.
Breakthrough Genomics, Breakthrough Genomics RCV004692081 SCV005191118 uncertain significance not provided criteria provided, single submitter not provided
Natera, Inc. RCV001830487 SCV002085466 uncertain significance Autosomal recessive DOPA responsive dystonia 2020-08-07 no assertion criteria provided clinical testing

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