Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV000006898 | SCV004047196 | pathogenic | Pyridoxal phosphate-responsive seizures | criteria provided, single submitter | clinical testing | The stop lost p.*262Qext*28 in PNPO (NM_018129.4) has been previously reported in homozygous form in individuals affected with Pyridoxamine 5'-phosphate oxidase deficiency. Expression studies in Chinese hamster ovary cells showed that the stop codon (X262Q) mutation was null activity mutation (Mills et al, 2005). The p.*262Qext*28 variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. The p.Ter262GlnextTer28 variant in the stop codon (Ter/*) at position 262, changing it to a Glutamine-codon (a no-stop variant) and adding a tail of new amino acids to the protein’s C-terminus, ending at a new stop codon (Ter/*) at position 28. The nucleotide c.784 in PNPO is predicted conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic. The observed variant was also detected in the spouse. | |
OMIM | RCV000006898 | SCV000027094 | pathogenic | Pyridoxal phosphate-responsive seizures | 2005-04-15 | no assertion criteria provided | literature only |