ClinVar Miner

Submissions for variant NM_000532.5(PCCB):c.1316A>G (p.Tyr439Cys) (rs769521436)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000490483 SCV000792715 likely pathogenic Propionyl-CoA carboxylase deficiency 2017-07-20 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000490483 SCV000919959 pathogenic Propionyl-CoA carboxylase deficiency 2018-06-07 criteria provided, single submitter clinical testing Variant summary: PCCB c.1316A>G (p.Tyr439Cys) results in a non-conservative amino acid change located in the Acetyl-coenzyme A carboxyltransferase, C-terminal domain (IPR011763) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 246228 control chromosomes, mostly occuring in the East Asian subpopulation. c.1316A>G has been reported in the literature in individuals affected with Propionic Acidemia; all of these cases were found in East Asian populations (Kim 2002, Yorifuji 2002, Chiu 2014). These data indicate that the variant is likely to be associated with disease. These publications also reported a significantly decreased enzyme activity in the affected individuals, with the most pronounced variant effect resulting in <10% of normal activity. A recent population study demonstrated a founder effect for the variant in the Korean population based on haplotype analysis (Park 2016). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Soonchunhyang University Bucheon Hospital,Soonchunhyang University Medical Center RCV000490483 SCV000267437 likely pathogenic Propionyl-CoA carboxylase deficiency 2016-03-18 criteria provided, single submitter reference population

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