ClinVar Miner

Submissions for variant NM_000282.4(PCCA):c.229C>T (p.Arg77Trp) (rs141371306)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665579 SCV000789725 likely pathogenic Propionyl-CoA carboxylase deficiency 2017-02-15 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000665579 SCV000919957 pathogenic Propionyl-CoA carboxylase deficiency 2018-11-29 criteria provided, single submitter clinical testing Variant summary: PCCA c.229C>T (p.Arg77Trp) results in a non-conservative amino acid change located in the Biotin carboxylation domain & Biotin carboxylase-like, N-terminal domain 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 245438 control chromosomes (gnomAD). c.229C>T has been reported in the literature in individuals affected with Propionic Acidemia (Chiu_2014, Perez_2010, Yang_2004, Perez-Cerda_2000). These data indicate that the variant is likely to be associated with disease. Experimental evidence reported in a publication evaluating an impact on protein function (Clavero_2002) demonstrated the variant to clearly diminish PCC activity (<10% of normal activity). A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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