ClinVar Miner

Submissions for variant NM_000532.5(PCCB):c.749A>G (p.His250Arg)

dbSNP: rs1933813724
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001055500 SCV001219897 likely pathogenic Propionic acidemia 2023-03-23 criteria provided, single submitter clinical testing This variant disrupts the p.His250 amino acid residue in PCCB. Other variant(s) that disrupt this residue have been observed in individuals with PCCB-related conditions (PMID: 30274917), which suggests that this may be a clinically significant amino acid residue. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PCCB protein function. ClinVar contains an entry for this variant (Variation ID: 851161). This missense change has been observed in individual(s) with propionic acidemia (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 250 of the PCCB protein (p.His250Arg). 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.
Natera, Inc. RCV001055500 SCV001454519 uncertain significance Propionic acidemia 2020-09-16 no assertion criteria provided clinical testing

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.