ClinVar Miner

Submissions for variant NM_022445.4(TPK1):c.169G>A (p.Glu57Lys)

gnomAD frequency: 0.00003  dbSNP: rs200717734
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001766886 SCV001989838 uncertain significance not provided 2019-05-21 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 that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV001882860 SCV002312774 uncertain significance Childhood encephalopathy due to thiamine pyrophosphokinase deficiency 2022-01-13 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 57 of the TPK1 protein (p.Glu57Lys). This variant is present in population databases (rs200717734, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TPK1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1305933). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.

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