Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000686636 | SCV000814163 | uncertain significance | Propionic acidemia | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 304 of the PCCB protein (p.Thr304Ile). This variant is present in population databases (rs147538201, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with PCCB-related conditions. ClinVar contains an entry for this variant (Variation ID: 566744). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PCCB protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Fulgent Genetics, |
RCV000686636 | SCV000895534 | uncertain significance | Propionic acidemia | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000686636 | SCV003812343 | uncertain significance | Propionic acidemia | 2022-12-13 | criteria provided, single submitter | clinical testing | |
Gene |
RCV003222100 | SCV003918727 | uncertain significance | not provided | 2023-04-09 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Natera, |
RCV000686636 | SCV001454521 | uncertain significance | Propionic acidemia | 2020-09-16 | no assertion criteria provided | clinical testing |