ClinVar Miner

Submissions for variant NM_000282.4(PCCA):c.1288C>T (p.Arg430Ter)

dbSNP: rs776821944
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001055670 SCV001220070 pathogenic Propionic acidemia 2023-04-06 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 851298). This premature translational stop signal has been observed in individual(s) with clinical features of propionic acidemia (PMID: 24059531). This variant is present in population databases (rs776821944, gnomAD 0.005%). This sequence change creates a premature translational stop signal (p.Arg430*) in the PCCA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PCCA are known to be pathogenic (PMID: 15464417).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001055670 SCV003928914 pathogenic Propionic acidemia 2023-04-04 criteria provided, single submitter clinical testing Variant summary: PCCA c.1288C>T (p.Arg430X) 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. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 250312 control chromosomes. c.1288C>T has been reported in the literature in individuals affected with Propionic Acidemia. These data indicate that the variant may be associated with disease. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV001055670 SCV004202893 pathogenic Propionic acidemia 2023-03-30 criteria provided, single submitter clinical testing

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