ClinVar Miner

Submissions for variant NM_000532.5(PCCB):c.1229G>A (p.Arg410Gln) (rs778742647)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000673426 SCV000798627 uncertain significance Propionyl-CoA carboxylase deficiency 2018-03-15 criteria provided, single submitter clinical testing
Invitae RCV000673426 SCV000960283 likely pathogenic Propionyl-CoA carboxylase deficiency 2018-12-31 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 410 of the PCCB protein (p.Arg410Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs778742647, ExAC 0.01%). This variant has been observed as homozygous or in combination with another PCCB variant in several individuals affected with propionic acidemia (PMID: 19238581, 24916042). ClinVar contains an entry for this variant (Variation ID: 557302). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Arg410 amino acid residue in PCCB. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 8411997, 12007220, 22033733, 15949719, 12757933, 15890657), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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