ClinVar Miner

Submissions for variant NM_000204.5(CFI):c.1016G>A (p.Arg339Gln)

gnomAD frequency: 0.00001  dbSNP: rs773085612
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001915496 SCV002176080 uncertain significance not provided 2023-06-15 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. Experimental studies have shown that this missense change affects CFI function (PMID: 32908800, 35069568). 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. ClinVar contains an entry for this variant (Variation ID: 1399319). This missense change has been observed in individual(s) with macular degeneration (PMID: 32908800, 35069568). This variant is present in population databases (rs773085612, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 339 of the CFI protein (p.Arg339Gln).
Mayo Clinic Laboratories, Mayo Clinic RCV001915496 SCV002542093 uncertain significance not provided 2021-10-07 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002482767 SCV002785078 uncertain significance Atypical hemolytic-uremic syndrome with I factor anomaly; Age related macular degeneration 13; Factor I deficiency 2021-12-23 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004526157 SCV005040436 uncertain significance not specified 2024-03-04 criteria provided, single submitter clinical testing Variant summary: CFI c.1016G>A (p.Arg339Gln) results in a conservative amino acid change located in the Serine proteases, trypsin domain (IPR001254) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251348 control chromosomes. c.1016G>A has been reported in the literature in individuals affected with age related Macular Degeneration (Java_2020, de Jong_2021). These reports do not provide unequivocal conclusions about association of the variant with Complement Factor I Deficiency. At least one publication reports experimental evidence evaluating an impact on protein function indicating that this variant affects function (Java_2020, de Jong_2021). The following publications have been ascertained in the context of this evaluation (PMID: 32908800, 35069568). ClinVar contains an entry for this variant (Variation ID: 1399319). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

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