ClinVar Miner

Submissions for variant NM_000282.4(PCCA):c.1430G>T (p.Gly477Val)

gnomAD frequency: 0.00001  dbSNP: rs776355907
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000664973 SCV000940073 pathogenic Propionic acidemia 2023-10-12 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 477 of the PCCA protein (p.Gly477Val). RNA analysis indicates that this missense change induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of propionic acidemia (PMID: 17051315; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 550273). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Studies have shown that this missense change results in skipping of exon 17, but is expected to preserve the integrity of the reading-frame (PMID: 17051315). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV000664973 SCV002060253 uncertain significance Propionic acidemia 2021-11-08 criteria provided, single submitter clinical testing NM_000282.3(PCCA):c.1430G>T(G477V) is a missense variant classified as a variant of uncertain significance in the context of PCCA-related propionic acidemia. G477V has been observed in cases with relevant disease (PMID: 17051315). Functional assessments of this variant are not available in the literature. G477V has not been observed in population frequency databases. In summary, there is insufficient evidence to classify NM_000282.3(PCCA):c.1430G>T(G477V) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening.

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