ClinVar Miner

Submissions for variant NM_000282.4(PCCA):c.805C>T (p.His269Tyr)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services,Murdoch Childrens Research Institute RCV001089988 SCV001244980 likely pathogenic Propionic acidemia 2018-06-17 criteria provided, single submitter clinical testing A homozygous missense variant, NM_000282.3(PCCA):c.805C>T has been identified in exon 10 of 24 of the PCCA gene. The variant is predicted to result in a moderate amino acid change from histidine to tyrosine at position 269 of the protein (NP_000273.2(PCCA):p.(His269Tyr)). The histidine residue at this position has very high conservation (100 vertebrates, UCSC), and is located within the CPSase_L_D2, ATP grasp and biotin carboxylation domain. In-silico predictions for this variant are consistently pathogenic (Polyphen, SIFT, CADD, Mutation Taster). The variant is absent in population databases (gnomAD, dbSNP, 1000G). This variant has not been previously reported in clinical cases. A different variant in the same codon resulting in a change to arginine has been reported as likely pathogenic (ClinVar). Analysis of parental samples indicated this variant is inherited from both parents. Based on the information available at the time of curation, 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.