ClinVar Miner

Submissions for variant NM_000360.4(TH):c.917G>A (p.Arg306His)

dbSNP: rs28934580
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000013121 SCV000800575 uncertain significance Autosomal recessive DOPA responsive dystonia 2017-08-11 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000013121 SCV002238974 pathogenic Autosomal recessive DOPA responsive dystonia 2023-10-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 337 of the TH protein (p.Arg337His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with infantile parkinsonism (PMID: 11246459). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is also known as R306H. ClinVar contains an entry for this variant (Variation ID: 12328). 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: 15468323, 24753243). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000013121 SCV004203870 likely pathogenic Autosomal recessive DOPA responsive dystonia 2023-04-25 criteria provided, single submitter clinical testing
OMIM RCV000013121 SCV000033368 pathogenic Autosomal recessive DOPA responsive dystonia 2000-01-01 no assertion criteria provided literature only

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