ClinVar Miner

Submissions for variant NM_000532.5(PCCB):c.990dup (p.Glu331Ter)

dbSNP: rs786200983
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000153647 SCV000239123 pathogenic not provided 2020-02-18 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 22033733, 24516753, 24059531, 23430860, 20549364, 12559849, 30705822, 31916709)
Invitae RCV000173704 SCV000631920 pathogenic Propionic acidemia 2024-01-22 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu331*) in the PCCB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PCCB are known to be pathogenic (PMID: 15464417). This variant is present in population databases (rs763069936, gnomAD 0.1%). This premature translational stop signal has been observed in individuals with propionic aciduria (PMID: 12559849, 22033733, 23430860, 24516753). ClinVar contains an entry for this variant (Variation ID: 167423). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000173704 SCV000697273 pathogenic Propionic acidemia 2017-07-24 criteria provided, single submitter clinical testing Variant summary: The PCCB c.990dupT (p.Glu331X) 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.This variant was found in 6/121406 control chromosomes at a frequency of 0.0000494, which does not exceed the estimated maximal expected allele frequency of a pathogenic PCCB variant (0.0025). Multiple publications have cited the variant in affected compound heterozygote and homozygote individuals. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Eurofins Ntd Llc (ga) RCV000153647 SCV000700506 pathogenic not provided 2017-03-02 criteria provided, single submitter clinical testing
Baylor Genetics RCV000173704 SCV001162959 pathogenic Propionic acidemia criteria provided, single submitter clinical testing
New York Genome Center RCV000173704 SCV002097857 pathogenic Propionic acidemia 2021-01-21 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000173704 SCV002811715 pathogenic Propionic acidemia 2022-03-31 criteria provided, single submitter clinical testing
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego RCV000173704 SCV004046091 pathogenic Propionic acidemia criteria provided, single submitter clinical testing This nonsense variant found in exon 11 of 16 is predicted to result in loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay (NMD). This variant has been previously reported as both a compound heterozygous and homozygous change in patients with propionic acidemia (MIM#: 606054; PMID: 12559849, 22033733, 23430860, 24516753). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.0008% (25/282848) and thus is presumed to be rare. Based on the available evidence, the c.1050dup (p.Glu351Ter) variant is classified as Pathogenic.
Counsyl RCV000173704 SCV001132452 pathogenic Propionic acidemia 2016-12-27 no assertion criteria provided clinical testing
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City RCV000173704 SCV001132883 pathogenic Propionic acidemia 2019-01-29 no assertion criteria provided clinical testing
Natera, Inc. RCV000173704 SCV001454523 pathogenic Propionic acidemia 2020-09-16 no assertion criteria provided clinical testing
Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) RCV000173704 SCV003927927 pathogenic Propionic acidemia 2023-04-01 no assertion criteria provided clinical testing

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