ClinVar Miner

Submissions for variant NM_000204.5(CFI):c.148C>G (p.Pro50Ala)

gnomAD frequency: 0.00006  dbSNP: rs144082872
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001144251 SCV001304840 uncertain significance Atypical hemolytic-uremic syndrome with I factor anomaly 2017-04-28 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 (formerly Invitae), Labcorp RCV001858947 SCV002139195 uncertain significance not provided 2023-12-10 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 50 of the CFI protein (p.Pro50Ala). This variant is present in population databases (rs144082872, gnomAD 0.03%). This missense change has been observed in individual(s) with atypical hemolytic uremic syndrome and age-related macular degeneration (PMID: 20016463, 24034049, 24036952, 31249236). ClinVar contains an entry for this variant (Variation ID: 899590). 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 80%. Experimental studies have shown that this missense change affects CFI function (PMID: 35069568). 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.

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