Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000664635 | SCV000788633 | uncertain significance | Propionic acidemia | 2017-12-27 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000664635 | SCV001136608 | uncertain significance | Propionic acidemia | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000664635 | SCV004293512 | likely pathogenic | Propionic acidemia | 2023-09-14 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 204 of the PCCB protein (p.Ala204Val). This variant is present in population databases (rs760499581, gnomAD 0.009%). This missense change has been observed in individual(s) with propionic acidemia (PMID: 28853722). ClinVar contains an entry for this variant (Variation ID: 203889). 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. |