ClinVar Miner

Submissions for variant NM_000186.4(CFH):c.3643C>G (p.Arg1215Gly)

dbSNP: rs121913051
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
OMIM RCV000018008 SCV000038287 risk factor Hemolytic uremic syndrome, atypical, susceptibility to, 1 2003-04-01 no assertion criteria provided literature only
Sydney Genome Diagnostics, Children's Hospital Westmead RCV001328244 SCV001449222 pathogenic Atypical hemolytic-uremic syndrome 2017-10-25 no assertion criteria provided clinical testing This individual is heterozygous for the c.3643C>G variant in the CFH gene. The c.3643C>G variant has not been reported in any population databases (i.e. gnomAD, ExAC or ESP). This variant has been previously described in the literature and the FH aHUS Mutation Database (http://www.fh-hus.org/fullList.php?protein=FH). In particular, this variant (first reported as R1197G, then R1215G) has been reported in the heterozygous state in multiple affected individuals in a large pedigree, including two individuals with first presentation at 5 months (Edelsten and Tuck 1978 Arch Dis Child 53:255-256; Warwicker et al 1998 Kidney International 53: 836-844; Sansbury et al 2014 Med Genet 51:756-764). The pedigree supported an autosomal dominant mode of inheritance, with incomplete penetrance. In vitro analysis of the p.Arg1215Gly mutant protein showed significant impact on protein function, indicative of loss-of-function (Jozsi et al 2006 J Am Soc Nephrol 17:170-177; Ferreira et al 2009 J Immunol 192:7009-7018). This variant is considered to be pathogenic 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.