ClinVar Miner

Submissions for variant NM_022445.4(TPK1):c.434C>T (p.Ala145Val)

gnomAD frequency: 0.00002  dbSNP: rs576168961
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001070168 SCV001235384 uncertain significance Childhood encephalopathy due to thiamine pyrophosphokinase deficiency 2024-02-26 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 145 of the TPK1 protein (p.Ala145Val). This variant is present in population databases (rs576168961, gnomAD 0.03%). 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: 863245). 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 not expected to disrupt TPK1 protein function with a negative predictive value of 80%. 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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