ClinVar Miner

Submissions for variant NM_022445.4(TPK1):c.10G>A (p.Ala4Thr)

gnomAD frequency: 0.00003  dbSNP: rs766958215
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001056275 SCV001220709 uncertain significance Childhood encephalopathy due to thiamine pyrophosphokinase deficiency 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 4 of the TPK1 protein (p.Ala4Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs766958215, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with TPK1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.

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