ClinVar Miner

Submissions for variant NM_000282.4(PCCA):c.878A>G (p.Gln293Arg) (rs879253805)

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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 RCV000236234 SCV000256843 pathogenic Propionic acidemia 2013-01-01 criteria provided, single submitter research
Invitae RCV000236234 SCV000954494 uncertain significance Propionic acidemia 2018-10-04 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 293 of the PCCA protein (p.Gln293Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be homozygous or in combination with another PCCA variant in individuals affected with propionic acidemia (PMID: 23430860, 27227689, Invitae). ClinVar contains an entry for this variant (Variation ID: 218252). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). The observation of one or more missense substitutions at this codon (p.Gln293Arg and p.Gln293Glu) in affected individuals suggests that this may be a clinically significant residue (PMID: 23430860, 27227689, 15164333). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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