Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002572762 | SCV002939007 | uncertain significance | not provided | 2024-09-18 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 856 of the C3 protein (p.Gln856Arg). This variant is present in population databases (rs765023130, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with C3-related conditions. ClinVar contains an entry for this variant (Variation ID: 1902305). 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) indicates that this missense variant is not expected to disrupt C3 protein function with a negative predictive value of 80%. 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. |
| Ambry Genetics | RCV004965912 | SCV005547139 | uncertain significance | Inborn genetic diseases | 2024-11-07 | criteria provided, single submitter | clinical testing | The c.2567A>G (p.Q856R) alteration is located in exon 20 (coding exon 20) of the C3 gene. This alteration results from a A to G substitution at nucleotide position 2567, causing the glutamine (Q) at amino acid position 856 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV005019241 | SCV005647584 | uncertain significance | Age related macular degeneration 9; Atypical hemolytic-uremic syndrome with C3 anomaly; Complement component 3 deficiency | 2024-06-18 | criteria provided, single submitter | clinical testing | |
| Prevention |
RCV003916487 | SCV004728145 | uncertain significance | C3-related disorder | 2023-12-20 | no assertion criteria provided | clinical testing | The C3 c.2567A>G variant is predicted to result in the amino acid substitution p.Gln856Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0062% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |