Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001993198 | SCV002237176 | pathogenic | not provided | 2024-01-09 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 258 of the CFI protein (p.Ala258Thr). RNA analysis indicates that this missense change induces altered splicing and likely results in a shortened protein product. This variant is present in population databases (rs199688124, gnomAD 0.02%). This missense change has been observed in individual(s) with CFI-related conditions (PMID: 8613545, 18374984, 22710145, 26826462, 29888403). It has also been observed to segregate with disease in related individuals. This variant is also known as 801-A. ClinVar contains an entry for this variant (Variation ID: 1451295). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this missense change results in skipping of exon 5, but is expected to preserve the integrity of the reading-frame (PMID: 8613545, 18374984). For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV002507693 | SCV002809313 | likely pathogenic | Atypical hemolytic-uremic syndrome with I factor anomaly; Age related macular degeneration 13; Factor I deficiency | 2022-03-31 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV001993198 | SCV004226768 | pathogenic | not provided | 2023-01-30 | criteria provided, single submitter | clinical testing | PP4, PM3_strong, PVS1_strong |
OMIM | RCV002074443 | SCV000033143 | pathogenic | Factor I deficiency | 1996-02-15 | no assertion criteria provided | literature only | |
Prevention |
RCV004542199 | SCV004779220 | pathogenic | CFI-related disorder | 2024-02-13 | no assertion criteria provided | clinical testing | The CFI c.772G>A variant is predicted to result in the amino acid substitution p.Ala258Thr. This variant was reported in individuals with complement factor I deficiency, aHUS, and age-related macular degeneration (see for example - Seddon et al. 2013. PubMed ID: 24036952; de Jong et al. 2020. PubMed ID: 32510551; Naesens et al. 2020. PubMed ID: 32853637; Java et al. 2020. PubMed ID: 32908800; Khan et al. 2021. PubMed ID: 34153144). This variant is the final nucleotide of the exon and functional studies found this variant causes exon skipping (Ponce-Castro et al. 2008. PubMed ID: 18374984). This variant is reported in 0.024% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as pathogenic. |