ClinVar Miner

Submissions for variant NM_000532.5(PCCB):c.494G>A (p.Arg165Gln) (rs1304714042)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666130 SCV000790374 likely pathogenic Propionyl-CoA carboxylase deficiency 2017-03-17 criteria provided, single submitter clinical testing
Invitae RCV000666130 SCV000941854 pathogenic Propionyl-CoA carboxylase deficiency 2018-09-27 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 165 of the PCCB protein (p.Arg165Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with propionic acidemia (PMID: 11749052, 12757933). Experimental studies have shown that this missense change abrogates PCCB enzymatic activity (PMID: 12757933). This variant disrupts the p.Arg165 amino acid residue in PCCB. Other variants that disrupt this residue have been observed in affected individuals (PMID: 20549364, 8295402, 15949719, 11749052, 12757933), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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