Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000479573 | SCV000568859 | uncertain significance | not provided | 2016-04-06 | criteria provided, single submitter | clinical testing | The V152M variant in the CFI gene has been reported previously in association with atypical hemolytic uricemic syndrome, and has also been seen in two individuals with advanced age-related macular degeneration (Westra et al., 2010; Seddon et al., 2013). This variant was not observed at any significant frequency in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The V152M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret V152M as a variant of uncertain significance. |
| Illumina Laboratory Services, |
RCV001150340 | SCV001311400 | uncertain significance | Atypical hemolytic-uremic syndrome with I factor anomaly | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Labcorp Genetics |
RCV000479573 | SCV002176245 | uncertain significance | not provided | 2024-01-07 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 152 of the CFI protein (p.Val152Met). This variant is present in population databases (rs367677199, gnomAD 0.008%). This missense change has been observed in individual(s) with age related macular degeneration, atypical hemolytic uremic syndrome, C3 glomerulopathy, and/or low serum FI (PMID: 20106822, 27268256, 29888403, 31440263, 32510551). ClinVar contains an entry for this variant (Variation ID: 420176). 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 expected to disrupt CFI protein function with a positive predictive value of 95%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on CFI function (PMID: 28282489, 32510551). 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, |
RCV002489157 | SCV002799534 | uncertain significance | Atypical hemolytic-uremic syndrome with I factor anomaly; Age related macular degeneration 13; Factor I deficiency | 2022-02-23 | criteria provided, single submitter | clinical testing |