ClinVar Miner

Submissions for variant NM_000204.5(CFI):c.1268C>A (p.Ala423Glu)

gnomAD frequency: 0.00004  dbSNP: rs555832641
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002542858 SCV003268170 uncertain significance not provided 2022-06-15 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. 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 not expected to disrupt CFI protein function. ClinVar contains an entry for this variant (Variation ID: 988224). This missense change has been observed in individual(s) with atypical hemolytic uremia (PMID: 27268256, 31900968). This variant is present in population databases (rs555832641, gnomAD 0.03%). This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 423 of the CFI protein (p.Ala423Glu).
Sydney Genome Diagnostics, Children's Hospital Westmead RCV001328251 SCV001449229 uncertain significance Atypical hemolytic-uremic syndrome 2018-08-22 no assertion criteria provided clinical testing This individual is heterozygous for the c.1268C>A variant in the CFI gene. To our knowledge, this variant has not been previously reported in the literature or any disease specific databases to be a disease causing variant. This variant has been reported in the gnomAD browser (http://gnomad.broadinstitute.org) with a very low allele frequency of 0.002% (6 out of 277,070 alleles). In silico analysis of pathogenicity (through Alamut Visual v2.8.1) using PolyPhen2, SIFT and MutationTaster suggest that this variant does not affect protein function and is likely to be benign. However, this analysis alone cannot be used to exclude pathogenicity. This variant is considered to be a variant of uncertain clinical significance (VOUS) according to the ACMG guidelines.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.