ClinVar Miner

Submissions for variant NM_000532.5(PCCB):c.774C>G (p.His258Gln) (rs141615209)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000874732 SCV001016952 likely benign Propionic acidemia 2020-11-21 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001192545 SCV001360758 likely benign not specified 2019-02-07 criteria provided, single submitter clinical testing Variant summary: PCCB c.774C>G (p.His258Gln) results in a non-conservative amino acid change located in the Acetyl-coenzyme A carboxyltransferase, N-terminal domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00054 in 277206 control chromosomes, predominantly at a frequency of 0.0049 within the African subpopulation in the gnomAD database. The observed variant frequency within African control individuals in the gnomAD database is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in PCCB causing Propionic Acidemia phenotype (0.0025), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.774C>G in individuals affected with Propionic Acidemia and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely benign.
GeneDx RCV001547426 SCV001767131 uncertain significance not provided 2020-06-08 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV000874732 SCV001460370 uncertain significance Propionic acidemia 2019-11-11 no assertion criteria provided clinical testing

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