ClinVar Miner

Submissions for variant NM_000532.5(PCCB):c.1495C>T (p.Arg499Ter)

gnomAD frequency: 0.00001  dbSNP: rs202247820
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000032127 SCV000697270 pathogenic Propionic acidemia 2017-05-23 criteria provided, single submitter clinical testing Variant summary: The PCCB c.1495C>T (p.Arg499X) variant results in a premature termination codon, predicted to cause a truncated or absent PCCB protein due to nonsense mediated decay, which are commonly known mechanisms for disease. A functional study, Chloupkova_2000 indicates that the variant impedes protein function and stability. This variant is absent in 121316 control chromosomes (ExAC). Multiple publications have cited the variant in affected compound heterozygous individuals, predominantly of Japan origin. In addition, multiple databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Counsyl RCV000032127 SCV000794409 pathogenic Propionic acidemia 2017-09-26 criteria provided, single submitter clinical testing
Invitae RCV000032127 SCV000960094 pathogenic Propionic acidemia 2024-01-11 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg499*) in the PCCB gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 41 amino acid(s) of the PCCB protein. This variant is present in population databases (rs202247820, gnomAD 0.0009%). This premature translational stop signal has been observed in individuals with propionic acidemia (PMID: 8295402, 12007220, 12189489). ClinVar contains an entry for this variant (Variation ID: 38878). 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.
CeGaT Center for Human Genetics Tuebingen RCV001090670 SCV001246346 pathogenic not provided 2017-05-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000032127 SCV002800755 pathogenic Propionic acidemia 2022-04-19 criteria provided, single submitter clinical testing
Baylor Genetics RCV000032127 SCV004205230 pathogenic Propionic acidemia 2023-03-04 criteria provided, single submitter clinical testing
GeneReviews RCV000032127 SCV000055682 not provided Propionic acidemia no assertion provided literature only
Natera, Inc. RCV000032127 SCV002081497 pathogenic Propionic acidemia 2020-09-12 no assertion criteria provided clinical testing

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