Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000782235 | SCV002282199 | uncertain significance | not provided | 2024-11-06 | 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 478 of the C3 protein (p.Arg478Leu). This variant is present in population databases (rs747968673, gnomAD 0.004%). This missense change has been observed in individual(s) with atypical hemolytic uremic syndrome (PMID: 20595690, 25608561). This variant is also known as R456L. ClinVar contains an entry for this variant (Variation ID: 633671). Invitae Evidence 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 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 C3 protein function. Experimental studies have shown that this missense change does not substantially affect C3 function (PMID: 25608561). 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, |
RCV002507351 | SCV002814693 | uncertain significance | Age related macular degeneration 9; Atypical hemolytic-uremic syndrome with C3 anomaly; Complement component 3 deficiency | 2024-02-29 | criteria provided, single submitter | clinical testing | |
| Gharavi Laboratory, |
RCV000782235 | SCV000920724 | uncertain significance | not provided | 2018-09-16 | no assertion criteria provided | research |