Submissions for variant NM_000204.5(CFI):c.1322A>G (p.Lys441Arg)

gnomAD frequency: 0.00243  dbSNP: rs41278047

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000325590	SCV000446871	benign	Atypical hemolytic-uremic syndrome with I factor anomaly	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001512909	SCV001720409	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
John Atkinson Laboratory, Washington University School of Medicine in St. Louis	RCV001849181	SCV001905510	likely benign	Thrombotic microangiopathy	2015-06-20	criteria provided, single submitter	clinical testing
Mendelics	RCV001528675	SCV002518072	uncertain significance	not specified	2022-05-04	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002294306	SCV002587699	benign	Atypical hemolytic-uremic syndrome	2020-03-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002520195	SCV003701554	likely benign	Inborn genetic diseases	2021-11-15	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224266	SCV003919789	likely benign	Atypical hemolytic-uremic syndrome with I factor anomaly; Age related macular degeneration 13; Factor I deficiency	2022-06-27	criteria provided, single submitter	clinical testing	This variant is present in the Genome Aggregation Database (Highest reported MAF: 4.8% [498/10368], including 17 homozygotes; https://gnomad.broadinstitute.org/variant/4-110667485-T-C?dataset=gnomad_r2_1). It is present in ClinVar (Variation ID: 347156). Evolutionary conservation and computational predictive tools are unclear for this variant. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign.
CeGaT Center for Human Genetics Tuebingen	RCV001512909	SCV004148683	likely benign	not provided	2023-01-01	criteria provided, single submitter	clinical testing	CFI: BP4, BS2
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528675	SCV001740816	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001512909	SCV001926990	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001512909	SCV001971168	likely benign	not provided		no assertion criteria provided	clinical testing