ClinVar Miner

Submissions for variant NM_000282.4(PCCA):c.742G>A (p.Glu248Lys)

dbSNP: rs1064793224
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000480056 SCV000565361 likely pathogenic not provided 2014-12-19 criteria provided, single submitter clinical testing A novel E248K variant that is likely pathogenic was identified in the PCCA gene. It has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The E248K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is highly conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, E248K is a strong candidate for a pathogenic variant, however the possibility that it is a benign variant cannot be excluded.
Invitae RCV002525770 SCV002989461 uncertain significance Propionic acidemia 2022-01-01 criteria provided, single submitter clinical testing 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PCCA protein function. ClinVar contains an entry for this variant (Variation ID: 418400). This variant has not been reported in the literature in individuals affected with PCCA-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 248 of the PCCA protein (p.Glu248Lys).

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