ClinVar Miner

Submissions for variant NM_000532.5(PCCB):c.1301C>T (p.Ala434Val)

gnomAD frequency: 0.00001  dbSNP: rs751538672
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670133 SCV000794950 likely pathogenic Propionic acidemia 2017-10-26 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000670133 SCV000931377 pathogenic Propionic acidemia 2024-04-22 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 434 of the PCCB protein (p.Ala434Val). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with propionic acidemia (PMID: 24863100). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 554490). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000670133 SCV001162960 pathogenic Propionic acidemia 2024-02-08 criteria provided, single submitter clinical testing
3billion RCV000670133 SCV002521852 pathogenic Propionic acidemia 2022-05-22 criteria provided, single submitter clinical testing The variant is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.002%). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.99; 3Cnet: 0.80). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000554490). The variant has been observed in multiple (>3) similarly affected unrelated individuals (PMID:24863100). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Natera, Inc. RCV000670133 SCV001454528 pathogenic 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.