Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Johns Hopkins Genomics, |
RCV001353352 | SCV001548502 | uncertain significance | Atypical hemolytic-uremic syndrome with B factor anomaly | 2021-03-29 | criteria provided, single submitter | clinical testing | CFB c.503C>T (rs779024832) is rare (<0.1%) in a large population dataset (gnomAD: 4/246460 total alleles; 0.00162%; no homozygotes) and has not been reported in ClinVar nor the literature, to our knowledge. Three bioinformatic tools queried predict that this substitution would be damaging and the proline residue at this position is evolutionarily conserved across most species assessed. We consider the clinical significance of c.503C>T to be uncertain at this time |
Labcorp Genetics |
RCV001871915 | SCV002287093 | uncertain significance | not provided | 2022-10-14 | criteria provided, single submitter | clinical testing | 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. 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 not expected to disrupt CFB protein function. ClinVar contains an entry for this variant (Variation ID: 1048765). This variant has not been reported in the literature in individuals affected with CFB-related conditions. This variant is present in population databases (rs779024832, gnomAD 0.007%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 168 of the CFB protein (p.Pro168Leu). |