ClinVar Miner

Submissions for variant NM_021830.5(TWNK):c.1628G>A (p.Arg543Gln)

dbSNP: rs753386843
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory of Inherited Metabolic Diseases, Research centre for medical genetics RCV000855763 SCV000998978 likely pathogenic Infantile onset spinocerebellar ataxia 2019-07-17 criteria provided, single submitter clinical testing
GeneDx RCV001759642 SCV001996954 uncertain significance not provided 2020-01-20 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
Invitae RCV001759642 SCV002981108 uncertain significance not provided 2022-11-08 criteria provided, single submitter clinical testing 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. 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) performed at Invitae indicates that this missense variant is expected to disrupt TWNK protein function. ClinVar contains an entry for this variant (Variation ID: 694432). This variant has not been reported in the literature in individuals affected with TWNK-related conditions. This variant is present in population databases (rs753386843, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 543 of the TWNK protein (p.Arg543Gln).

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