Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mayo Clinic Laboratories, |
RCV001843942 | SCV002103247 | pathogenic | not provided | 2022-01-04 | criteria provided, single submitter | clinical testing | PM1, PM2_supporting, PS2_moderate, PS3, PS4_moderate |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004528119 | SCV002511422 | pathogenic | CFH-related disorder | 2022-04-08 | criteria provided, single submitter | clinical testing | Variant summary: CFH c.3572C>T (p.Ser1191Leu) results in a non-conservative amino acid change located in the last (i.e. the C-terminal) sushi/SCR/CCP repeat domain (IPR000436) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 251154 control chromosomes (gnomAD v2.1). The variant, c.3572C>T, has been reported in the literature in several individuals (see HGMD, OMIM), who were affected with atypical hemolytic uremic syndrome (aHUS); notably, in a proportion of the reported cases this variant occurred in combination with Val1197Ala (including 2 proven de novo cases), as a result of a gene conversion event (see Heinen_2006). Publications reported experimental evidence evaluating an impact on protein function, and demonstrated that the variant in isolation resulted in defects of activities characteristic for the functions of C-terminal region of the protein (Heinen_2006, Merinero_2021). Of note, the variant in combination (i.e. in cis) with Val1197Ala also was associated with a defective function (Heinen_2006). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Fulgent Genetics, |
RCV002496396 | SCV002807658 | pathogenic | Basal laminar drusen; Factor H deficiency; Hemolytic uremic syndrome, atypical, susceptibility to, 1; Age related macular degeneration 4 | 2024-01-08 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV003450644 | SCV004177474 | pathogenic | Factor H deficiency | 2023-04-11 | criteria provided, single submitter | clinical testing | |
Breakthrough Genomics, |
RCV000018011 | SCV005088850 | pathogenic | Hemolytic uremic syndrome, atypical, susceptibility to, 1 | 2020-10-08 | criteria provided, single submitter | clinical testing | This variant was previously reported in heterozygous, compound heterozygous and homozygous state in patients with atypical hemolytic uremic syndrome and was shown to segregate with the disease and classified as pathogenic [PMID: 10577907, 19854549, 19454698, 28596415, 20301541]. Functional studies showed the variant resulted in impaired C3b binding and a defective capacity to control complement activation on cellular surfaces [PMID: 16470555]. |
OMIM | RCV000018011 | SCV000038290 | risk factor | Hemolytic uremic syndrome, atypical, susceptibility to, 1 | 2000-05-01 | no assertion criteria provided | literature only | |
Gene |
RCV000018011 | SCV000040512 | not provided | Hemolytic uremic syndrome, atypical, susceptibility to, 1 | no assertion provided | literature only |