ClinVar Miner

Submissions for variant NM_033453.4(ITPA):c.452G>A (p.Trp151Ter)

gnomAD frequency: 0.00001  dbSNP: rs200086262
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 RCV000578901 SCV000680817 pathogenic not provided 2017-11-10 criteria provided, single submitter clinical testing The W151X variant has been previously reported in the homozygous state in two siblings with progressive microcephaly, seizures, and developmental delay; ITPase activity in erythrocytes of one of the siblings was found to be severely reduced (Kevelam et. al., 2015). The W151X variant is observed in 11/25636 (0.04%) alleles from individuals of Finnish background, in large population cohorts (Lek et al., 2016). This nonsense variant is predicted to cause loss of normal protein function through protein truncation as the last 44 amino acids are lost. Therefore, we interpret W151X as a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV000640526 SCV000762118 pathogenic Inosine triphosphatase deficiency 2024-11-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp151*) in the ITPA gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 44 amino acid(s) of the ITPA protein. This variant is present in population databases (rs200086262, gnomAD 0.04%). This premature translational stop signal has been observed in individuals with ITPA-related conditions (PMID: 26224535, 30856165). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 218089). 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 ITPA protein in which other variant(s) (p.Arg178Cys) have been observed in individuals with ITPA-related conditions (PMID: 26224535). 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.
OMIM RCV000202318 SCV000257321 pathogenic Developmental and epileptic encephalopathy, 35 2015-10-01 no assertion criteria provided literature only

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.