ClinVar Miner

Submissions for variant NM_022445.4(TPK1):c.185+1G>A

gnomAD frequency: 0.00002  dbSNP: rs747753388
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000197327 SCV000252397 pathogenic not provided 2013-09-17 criteria provided, single submitter clinical testing c.185+1 G>A: IVS4+1 G>A in intron 4 of the TPK1 gene (NM_022445.3). The c.185+1 G>A splice site mutation in the TPK1 gene destroys the canonical splice donor site in intron 4. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Although this mutation has not been previously reported to our knowledge, it is expected to be a pathogenic mutation. The variant is found in LSME-MITOP panel(s).
Eurofins Ntd Llc (ga) RCV000197327 SCV000862934 likely pathogenic not provided 2018-08-14 criteria provided, single submitter clinical testing
Invitae RCV001853204 SCV002281596 likely pathogenic Childhood encephalopathy due to thiamine pyrophosphokinase deficiency 2023-11-19 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 of the TPK1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TPK1 are known to be pathogenic (PMID: 22152682, 25458521). This variant is present in population databases (rs747753388, gnomAD 0.002%). 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: 215274). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.