Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Medical Genetics and Genomics, |
RCV000236764 | SCV000256841 | pathogenic | Propionic acidemia | 2013-01-01 | criteria provided, single submitter | research | |
Counsyl | RCV000236764 | SCV000790934 | likely pathogenic | Propionic acidemia | 2017-10-04 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000236764 | SCV003442258 | likely pathogenic | Propionic acidemia | 2022-07-27 | criteria provided, single submitter | clinical testing | Disruption of this splice site has been observed in individual(s) with propionic acidemia (PMID: 27227689). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 19 of the PCCA gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PCCA are known to be pathogenic (PMID: 15464417). ClinVar contains an entry for this variant (Variation ID: 218250). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. |