ClinVar Miner

Submissions for variant NM_000532.5(PCCB):c.1127G>T (p.Arg376Leu)

dbSNP: rs142982097
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000674584 SCV000799946 uncertain significance Propionic acidemia 2018-05-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000674584 SCV003525287 likely pathogenic Propionic acidemia 2022-06-09 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 376 of the PCCB protein (p.Arg376Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Propionic Acidemia (PMID: 22033733). ClinVar contains an entry for this variant (Variation ID: 558333). 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 PCCB protein function. 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. This variant disrupts the p.Arg376 amino acid residue in PCCB. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19342984, 27900673). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing.

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