ClinVar Miner

Submissions for variant NM_000360.4(TH):c.1141C>A (p.Gln381Lys)

gnomAD frequency: 0.00001  dbSNP: rs121917762
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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 RCV000013117 SCV001574404 pathogenic Autosomal recessive DOPA responsive dystonia 2023-10-10 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 412 of the TH protein (p.Gln412Lys). This variant is present in population databases (rs121917762, gnomAD 0.0009%). This missense change has been observed in individuals with dopa-responsive dystonia (PMID: 7814018). It has also been observed to segregate with disease in related individuals. This variant is also known as Gln381Lys. ClinVar contains an entry for this variant (Variation ID: 12324). 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. Experimental studies have shown that this missense change affects TH function (PMID: 8528210, 8817341, 24753243, 26220941). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000013117 SCV004203856 likely pathogenic Autosomal recessive DOPA responsive dystonia 2024-03-02 criteria provided, single submitter clinical testing
OMIM RCV000013117 SCV000033364 pathogenic Autosomal recessive DOPA responsive dystonia 1999-06-01 no assertion criteria provided literature only

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