ClinVar Miner

Submissions for variant NM_005859.5(PURA):c.159dup (p.Leu54fs) (rs1554129040)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498606 SCV000589940 pathogenic not provided 2017-06-16 criteria provided, single submitter clinical testing The c.159dupG variant in the PURA gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.159dupG variant causes a frameshift starting with codon Leucine 54, changes this amino acid to an Alanine residue, and creates a premature Stop codon at position 147 of the new reading frame, denoted p.Leu54AlafsX147. This variant is predicted to cause loss of normal protein function through protein truncation. The c.159dupG variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.159dupG as a pathogenic variant.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000616762 SCV000712536 pathogenic PURA-related severe neonatal hypotonia-seizures-encephalopathy syndrome due to a point mutation 2016-11-18 criteria provided, single submitter clinical testing The p.Leu54fs variant in PURA has not been previously reported in individuals wi th severe neonatal hypotonia-seizures-encephalopathy syndrome. Data from large p opulation studies is insufficient to assess the frequency of this variant. The p .Leu54fs variant is predicted to cause a frameshift, which alters the protein?s amino acid sequence beginning at position 54 and leads to a premature terminatio n codon 147 amino acids downstream. This gene contains a single exon, so the alt ered transcript is more likely to escape nonsense mediated decay (NMD) and resul t in a truncated protein. Heterozygous truncating variants in the PURA gene are strongly associated with severe neonatal hypotonia-seizures-encephalopathy syndr ome, with the all causative variants reported to date occuring de novo. In summa ry, the p.Leu54fs variant meets criteria to be classified as pathogenic for seve re neonatal hypotonia-seizures-encephalopathy syndrome based on its predicted im pact to the protein.
Invitae RCV001035879 SCV001199218 pathogenic Mental retardation, autosomal dominant 31 2019-03-07 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the PURA gene (p.Leu54Alafs*147). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 269 amino acids of the PURA protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PURA-related conditions. ClinVar contains an entry for this variant (Variation ID: 432233). This variant disrupts the C-terminus of the PURA protein. Other variant(s) that disrupt this region (p.Asp207Thrfs*16, p.Phe243Tyrfs*50, p.Tyr261*) have been determined to be pathogenic (Invitae, PMID: 25342064, 25439098). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000498606 SCV001248354 pathogenic not provided 2019-09-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000498606 SCV001447067 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge RCV001003590 SCV001161967 likely pathogenic Intellectual disability no assertion criteria provided research

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.