ClinVar Miner

Submissions for variant NM_022445.4(TPK1):c.613+1G>C

dbSNP: rs760398697
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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 RCV000793670 SCV000933034 pathogenic Childhood encephalopathy due to thiamine pyrophosphokinase deficiency 2023-07-17 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 8 of the TPK1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is present in population databases (rs760398697, gnomAD 0.0009%). 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: 640613). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the TPK1 protein in which other variant(s) (p.Asn219Ser) have been determined to be pathogenic (PMID: 22152682, 28747443, 30483896). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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