Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001862429 | SCV002281790 | uncertain significance | not provided | 2022-07-19 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 458 of the CFB protein (p.Met458Ile). This variant is present in population databases (rs200837114, gnomAD 0.004%). This missense change has been observed in individual(s) with atypical hemolytic uremic syndrome (PMID: 20513133). This variant is also known as M433I. ClinVar contains an entry for this variant (Variation ID: 829990). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change affects CFB function (PMID: 24652797). 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. |
| Genome Diagnostics Laboratory, |
RCV002294435 | SCV002587663 | uncertain significance | Atypical hemolytic-uremic syndrome | 2020-07-01 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002481842 | SCV002778826 | uncertain significance | Atypical hemolytic-uremic syndrome with B factor anomaly; Age related macular degeneration 14; Complement factor b deficiency | 2021-11-01 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004689961 | SCV005185890 | uncertain significance | not specified | 2024-05-03 | criteria provided, single submitter | clinical testing | Variant summary: CFB c.1374G>A (p.Met458Ile; also known as M433I in the literature) results in a conservative amino acid change located in the von Willebrand factor, type A domain (IPR002035) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 247730 control chromosomes. c.1374G>A has been reported in the literature in individuals affected with genetic atypical hemolytic uremic syndrome (Maga_2010). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function and the authors of this report have characterized the variant as a gain -of-function mutation (Marinozzi_2014). The following publications have been ascertained in the context of this evaluation (PMID: 24799305, 24906628, 36591303, 24652797, 35267578).ClinVar contains an entry for this variant (Variation ID: 829990). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Bioscientia Institut fuer Medizinische Diagnostik Gmb |
RCV001029953 | SCV001192751 | pathogenic | Atypical hemolytic-uremic syndrome with B factor anomaly | 2019-07-02 | no assertion criteria provided | clinical testing |