ClinVar Miner

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

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Total submissions: 8
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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 likely benign Propionyl-CoA carboxylase deficiency 2016-06-14 criteria provided, single submitter clinical testing
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 Propionyl-CoA carboxylase deficiency 2017-04-06 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000313421 SCV000744069 likely benign Propionyl-CoA carboxylase deficiency 2014-10-09 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America 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.
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000313421 SCV000733195 benign Propionyl-CoA carboxylase deficiency no assertion criteria provided clinical testing

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