ClinVar Miner

Submissions for variant NM_000282.4(PCCA):c.1423A>G (p.Ile475Val) (rs35719359)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000078547 SCV000110403 benign not specified 2012-09-14 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000078547 SCV000303450 likely benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000313421 SCV000382015 benign Propionic acidemia 2018-03-06 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx RCV000078547 SCV000514038 benign not specified 2015-12-01 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000313421 SCV000631898 benign Propionic acidemia 2020-12-05 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000313421 SCV000744069 likely benign Propionic acidemia 2014-10-09 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000078547 SCV000919955 benign not specified 2018-03-29 criteria provided, single submitter clinical testing Variant summary: PCCA c.1423A>G (p.Ile475Val) results in a conservative amino acid change located in the Biotin carboxylase, C-terminal domain of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.043 in 277082 control chromosomes in the gnomAD database and literature, including 391 homozygotes. The observed variant frequency is approximately 12.53 fold of the estimated maximal expected allele frequency for a pathogenic variant in PCCA causing Propionic Acidemia phenotype (0.0034), strongly suggesting that the variant is benign. This variant has been reported in the literature in homozygous individuals affected with Propionic Acidemia but was also found in controls in the same study (Richard_1999). This report does not provide unequivocal conclusions about an association of the variant with Propionic Acidemia. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign (x2) and likely benign (x1). Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000313421 SCV001159024 benign Propionic acidemia 2020-07-04 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000313421 SCV000733195 benign Propionic acidemia no assertion criteria provided clinical testing
Natera, Inc. RCV000313421 SCV001455848 benign Propionic acidemia 2020-09-16 no assertion criteria provided clinical testing

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