ClinVar Miner

Submissions for variant NM_000282.4(PCCA):c.2129_2130del (p.Val710fs) (rs1317003529)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,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 uncertain significance Propionic acidemia 2019-10-24 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the PCCA gene (p.Val710Alafs*23). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 19 amino acids of the PCCA protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PCCA-related conditions. ClinVar contains an entry for this variant (Variation ID: 618775). Experimental studies and prediction algorithms are not available or were not evaluated for this variant, and the functional significance of the affected amino acid(s) is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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