Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000757595 | SCV000885886 | likely pathogenic | not provided | 2018-02-20 | criteria provided, single submitter | clinical testing | The c.2129_2130delTG variant has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. Nearby variants (c.2127delT and c.2133_2135delCTG) have been reported in patients with propionic acidemia and biochemically demonstrated to disrupt enzyme function (Campeau 1999 and Riemersma 2017). The c.2129_2130delTG variant creates a frameshift at codon 710 of the last exon (24 of 24) of the PCCA gene. This variant is in the biotin carboxyl carrier protein domain of PCCA, and is predicted to create a frameshifted, C-terminally extended polypeptide. It is listed in the Genome Aggregation Database (gnomAD) with a frequency of 0.01 percent in the Latino population (identified on 5 out of 33,582 chromosomes). Overall, the c.2129_2130delTG variant is considered to be likely pathogenic. |
| Invitae | RCV001228511 | SCV001400912 | pathogenic | Propionic acidemia | 2023-11-01 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Val710Alafs*23) in the PCCA gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 19 amino acid(s) of the PCCA protein. This variant is present in population databases (no rsID available, gnomAD 0.01%). This premature translational stop signal 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. ClinVar contains an entry for this variant (Variation ID: 618775). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant disrupts a region of the PCCA protein in which other variant(s) (p.Cys712del) have been observed in individuals with PCCA-related conditions (PMID: 10329019). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |