ClinVar Miner

Submissions for variant NM_000282.4(PCCA):c.863G>A (p.Arg288Lys) (rs879253810)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Medical Genetics and Genomics,Sir Ganga Ram Hospital RCV000236908 SCV000256853 pathogenic Propionic acidemia 2014-01-01 criteria provided, single submitter research
Invitae RCV000236908 SCV000631909 likely pathogenic Propionic acidemia 2016-08-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with lysine at codon 288 of the PCCA protein (p.Arg288Lys). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and lysine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to co-occur with another likely pathogenic or pathogenic PCCA variant in an individual affected with propionic acidemia in the literature (PMID: 27227689) as well as one individual tested at Invitae. ClinVar contains an entry for this variant (Variation ID: 21862). The arginine at codon position 288 falls in the biotin carboxylase domain of the PCCA protein and has been predicted as an important residue for the catalysis or substrate binding activities of the enzyme (PMID: 27227689, 7915138, 20725044). Further supporting the functional importance of this residue, experimental studies have shown that a different amino acid change at this position, p.Arg288Gly, impairs the activity of the enzyme (PMID: 20493181). However, the severity of impact of this particular variant p.Arg288Lys has not been determined by functional studies. For these reasons, this variant has been classified as Likely Pathogenic.

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