Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Institute of Medical Genetics and Genomics, |
RCV000235647 | SCV000256889 | pathogenic | Propionic acidemia | criteria provided, single submitter | research | ||
Counsyl | RCV000235647 | SCV000797713 | likely pathogenic | Propionic acidemia | 2018-02-07 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000235647 | SCV001219898 | pathogenic | Propionic acidemia | 2024-01-22 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg514*) in the PCCB gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 26 amino acid(s) of the PCCB protein. 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 premature translational stop signal has been observed in individuals with proprionic acidemia (PMID: 11136555, 24059531, 27227689). ClinVar contains an entry for this variant (Variation ID: 217893). 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000235647 | SCV001623158 | pathogenic | Propionic acidemia | 2021-05-13 | criteria provided, single submitter | clinical testing | Variant summary: PCCB c.1540C>T (p.Arg514X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4e-06 in 251236 control chromosomes. c.1540C>T has been reported in the literature in individuals affected with Propionic Acidemia (e.g. Sanchez-Alcudia_2012, Al-Jasmi_2016). These data indicate that the variant may be associated with disease. At least one publication reports that full-length protein is not detectable for PCCB with p.Arg514* (Sanchez-Alcudia_2012). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Fulgent Genetics, |
RCV000235647 | SCV002798016 | pathogenic | Propionic acidemia | 2022-05-08 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000235647 | SCV004205213 | pathogenic | Propionic acidemia | 2023-07-04 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV000235647 | SCV002081500 | pathogenic | Propionic acidemia | 2020-12-18 | no assertion criteria provided | clinical testing |