Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001247013 | SCV001420410 | likely pathogenic | Propionic acidemia | 2024-01-11 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 505 of the PCCB protein (p.Ile505Thr). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of propionic acidemia (Invitae). ClinVar contains an entry for this variant (Variation ID: 971266). 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%. 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. |
Ambry Genetics | RCV002568671 | SCV003575593 | uncertain significance | Inborn genetic diseases | 2021-10-12 | criteria provided, single submitter | clinical testing | The c.1514T>C (p.I505T) alteration is located in exon 15 (coding exon 15) of the PCCB gene. This alteration results from a T to C substitution at nucleotide position 1514, causing the isoleucine (I) at amino acid position 505 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Baylor Genetics | RCV001247013 | SCV004205181 | likely pathogenic | Propionic acidemia | 2023-10-18 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001247013 | SCV002081499 | uncertain significance | Propionic acidemia | 2021-05-03 | no assertion criteria provided | clinical testing |