Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000032127 | SCV000697270 | pathogenic | Propionic acidemia | 2017-05-23 | criteria provided, single submitter | clinical testing | Variant summary: The PCCB c.1495C>T (p.Arg499X) variant results in a premature termination codon, predicted to cause a truncated or absent PCCB protein due to nonsense mediated decay, which are commonly known mechanisms for disease. A functional study, Chloupkova_2000 indicates that the variant impedes protein function and stability. This variant is absent in 121316 control chromosomes (ExAC). Multiple publications have cited the variant in affected compound heterozygous individuals, predominantly of Japan origin. In addition, multiple databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. |
Counsyl | RCV000032127 | SCV000794409 | pathogenic | Propionic acidemia | 2017-09-26 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000032127 | SCV000960094 | pathogenic | Propionic acidemia | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg499*) in the PCCB gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 41 amino acid(s) of the PCCB protein. This variant is present in population databases (rs202247820, gnomAD 0.0009%). This premature translational stop signal has been observed in individuals with propionic acidemia (PMID: 8295402, 12007220, 12189489). ClinVar contains an entry for this variant (Variation ID: 38878). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects PCCB function (PMID: 11136555). For these reasons, this variant has been classified as Pathogenic. |
Ce |
RCV001090670 | SCV001246346 | pathogenic | not provided | 2017-05-01 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000032127 | SCV002800755 | pathogenic | Propionic acidemia | 2022-04-19 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000032127 | SCV004205230 | pathogenic | Propionic acidemia | 2023-03-04 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000032127 | SCV000055682 | not provided | Propionic acidemia | no assertion provided | literature only | ||
Natera, |
RCV000032127 | SCV002081497 | pathogenic | Propionic acidemia | 2020-09-12 | no assertion criteria provided | clinical testing |