ClinVar Miner

Submissions for variant NM_022445.4(TPK1):c.677T>A (p.Val226Asp)

gnomAD frequency: 0.00003  dbSNP: rs550639617
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000560878 SCV000652142 uncertain significance Childhood encephalopathy due to thiamine pyrophosphokinase deficiency 2021-09-07 criteria provided, single submitter clinical testing This sequence change replaces valine with aspartic acid at codon 226 of the TPK1 protein (p.Val226Asp). The valine residue is weakly conserved and there is a large physicochemical difference between valine and aspartic acid. This variant is present in population databases (rs550639617, ExAC 0.03%). 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 (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.
Ambry Genetics RCV004024218 SCV004970728 uncertain significance Inborn genetic diseases 2024-02-05 criteria provided, single submitter clinical testing The c.677T>A (p.V226D) alteration is located in exon 9 (coding exon 8) of the TPK1 gene. This alteration results from a T to A substitution at nucleotide position 677, causing the valine (V) at amino acid position 226 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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