ClinVar Miner

Submissions for variant NM_000532.5(PCCB):c.733G>A (p.Gly245Ser)

gnomAD frequency: 0.00001  dbSNP: rs756414710
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000790500 SCV002286883 pathogenic Propionic acidemia 2023-11-18 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 245 of the PCCB protein (p.Gly245Ser). This variant is present in population databases (rs756414710, gnomAD 0.01%). This missense change has been observed in individual(s) with proprionic acidemia (PMID: 33028371; 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: 638037). 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 with a positive predictive value of 80%. This variant disrupts the p.Gly245 amino acid residue in PCCB. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000790500 SCV002782381 pathogenic Propionic acidemia 2024-03-14 criteria provided, single submitter clinical testing
Baylor Genetics RCV000790500 SCV004205203 likely pathogenic Propionic acidemia 2023-12-29 criteria provided, single submitter clinical testing
Laboratory of Metabolic Disorders, Peking University First Hospital RCV000790500 SCV000929828 likely pathogenic Propionic acidemia 2019-05-08 no assertion criteria provided clinical testing

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