ClinVar Miner

Submissions for variant NM_000282.4(PCCA):c.615dup (p.Val206fs) (rs1566767338)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000778384 SCV000914606 uncertain significance Propionic acidemia 2017-09-12 criteria provided, single submitter clinical testing The PCCA c.615dupT (p.Val206CysfsTer30) variant results in a frameshift, and is predicted to result in premature termination of the protein.It was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018) and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene and cDNA change, and amino acid change. No publications were found based on this search. Due to the potential impact of frameshift variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for propionic acidemia.
Invitae RCV000778384 SCV001587327 pathogenic Propionic acidemia 2020-06-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val206Cysfs*30) in the PCCA gene. It is expected to result in an absent or disrupted protein product. 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: 631694). Loss-of-function variants in PCCA are known to be pathogenic (PMID: 15464417). For these reasons, this variant has been classified as Pathogenic.

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